메뉴 건너뛰기




Volumn 5, Issue 4, 2010, Pages 286-303

Flavivirus RNA cap methyltransferase: Structure, function, and inhibition

Author keywords

Flavivirus NS5; inhibitor; methyltransferase; RNA cap methylation; structure and function

Indexed keywords

FLAVIVIRUS; MUS; WEST NILE VIRUS;

EID: 77956126053     PISSN: 16733509     EISSN: 16733622     Source Type: Journal    
DOI: 10.1007/s11515-010-0660-y     Document Type: Review
Times cited : (63)

References (114)
  • 1
    • 0016741381 scopus 로고
    • The 5′ terminal structure of the methylated mRNA synthesized in vitro by vesicular stomatitis virus
    • Abraham G, Rhodes D P, Banerjee A K (1975). The 5′ terminal structure of the methylated mRNA synthesized in vitro by vesicular stomatitis virus. Cell, 5(1): 51-58.
    • (1975) Cell , vol.5 , Issue.1 , pp. 51-58
    • Abraham, G.1    Rhodes, D.P.2    Banerjee, A.K.3
  • 2
    • 0035955628 scopus 로고    scopus 로고
    • De novo synthesis of RNA by the dengue virus RNA-dependent RNA polymerase exhibits temperature dependence at the initiation but not elongation phase
    • Ackermann M, Padmanabhan R (2001). De novo synthesis of RNA by the dengue virus RNA-dependent RNA polymerase exhibits temperature dependence at the initiation but not elongation phase. J Biol Chem, 276(43): 39926-39937.
    • (2001) J Biol Chem , vol.276 , Issue.43 , pp. 39926-39937
    • Ackermann, M.1    Padmanabhan, R.2
  • 3
    • 0028833053 scopus 로고
    • Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP
    • Ahola T, Kääriäinen L (1995). Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP. Proc Natl Acad Sci U S A, 92(2): 507-511.
    • (1995) Proc Natl Acad Sci U S A , vol.92 , Issue.2 , pp. 507-511
    • Ahola, T.1    Kääriäinen, L.2
  • 4
    • 0027285404 scopus 로고
    • Dengue 2 virus NS2B and NS3 form a stable complex that can cleave NS3 within the helicase domain
    • Arias C F, Preugschat F, Strauss J H (1993). Dengue 2 virus NS2B and NS3 form a stable complex that can cleave NS3 within the helicase domain. Virology, 193(2): 888-899.
    • (1993) Virology , vol.193 , Issue.2 , pp. 888-899
    • Arias, C.F.1    Preugschat, F.2    Strauss, J.H.3
  • 5
    • 0034075352 scopus 로고    scopus 로고
    • The West Nile Virus outbreak of 1999 in New York: the Flushing Hospital experience
    • Asnis D S, Conetta R, Teixeira A A, Waldman G, Sampson B A (2000). The West Nile Virus outbreak of 1999 in New York: the Flushing Hospital experience. Clin Infect Dis, 30(3): 413-418.
    • (2000) Clin Infect Dis , vol.30 , Issue.3 , pp. 413-418
    • Asnis, D.S.1    Conetta, R.2    Teixeira, A.A.3    Waldman, G.4    Sampson, B.A.5
  • 6
    • 0035683662 scopus 로고    scopus 로고
    • The West Nile virus encephalitis outbreak in the United States (1999-2000): from Flushing, New York, to beyond its borders
    • Asnis D S, Conetta R, Waldman G, Teixeira A A (2001). The West Nile virus encephalitis outbreak in the United States (1999-2000): from Flushing, New York, to beyond its borders. Ann N Y Acad Sci, 951: 161-171.
    • (2001) Ann N Y Acad Sci , vol.951 , pp. 161-171
    • Asnis, D.S.1    Conetta, R.2    Waldman, G.3    Teixeira, A.A.4
  • 9
    • 0018265468 scopus 로고
    • mRNA(nucleoside-2′-)-methyltransferase from vaccinia virus. Characteristics and substrate specificity
    • Barbosa E, Moss B (1978). mRNA(nucleoside-2′-)-methyltransferase from vaccinia virus. Characteristics and substrate specificity. J Biol Chem, 253(21): 7698-7702.
    • (1978) J Biol Chem , vol.253 , Issue.21 , pp. 7698-7702
    • Barbosa, E.1    Moss, B.2
  • 10
    • 4143116991 scopus 로고    scopus 로고
    • A structural basis for the inhibition of the NS5 dengue virus mRNA 2′-O-methyltransferase domain by ribavirin 5′-triphosphate
    • Benarroch D, Egloff M P, Mulard L, Guerreiro C, Romette J L, Canard B (2004). A structural basis for the inhibition of the NS5 dengue virus mRNA 2′-O-methyltransferase domain by ribavirin 5′-triphosphate. J Biol Chem, 279(34): 35638-35643.
    • (2004) J Biol Chem , vol.279 , Issue.34 , pp. 35638-35643
    • Benarroch, D.1    Egloff, M.P.2    Mulard, L.3    Guerreiro, C.4    Romette, J.L.5    Canard, B.6
  • 11
    • 0035735238 scopus 로고    scopus 로고
    • West Nile virus activity in the United States, 2001
    • Bernard K A, Kramer L D (2001). West Nile virus activity in the United States, 2001. Viral Immunol, 14(4): 319-338.
    • (2001) Viral Immunol , vol.14 , Issue.4 , pp. 319-338
    • Bernard, K.A.1    Kramer, L.D.2
  • 13
    • 53249122878 scopus 로고    scopus 로고
    • Phosphorylation of yellow fever virus NS5 alters methyltransferase activity
    • Bhattacharya D, Hoover S, Falk S P, Weisblum B, Vestling M, Striker R (2008). Phosphorylation of yellow fever virus NS5 alters methyltransferase activity. Virology, 380(2): 276-284.
    • (2008) Virology , vol.380 , Issue.2 , pp. 276-284
    • Bhattacharya, D.1    Hoover, S.2    Falk, S.P.3    Weisblum, B.4    Vestling, M.5    Striker, R.6
  • 14
    • 0031572262 scopus 로고    scopus 로고
    • Viral and cellular enzymes involved in synthesis of mRNA cap structure
    • Bisaillon M, Lemay G (1997). Viral and cellular enzymes involved in synthesis of mRNA cap structure. Virology, 236(1): 1-7.
    • (1997) Virology , vol.236 , Issue.1 , pp. 1-7
    • Bisaillon, M.1    Lemay, G.2
  • 15
    • 77954956665 scopus 로고    scopus 로고
    • Bollati M, Alvarez K, Assenberg R, Baronti C, Canard B, Cook S, Coutard B, Decroly E, de Lamballerie X, Gould E A, Grard G, Grimes J M, Hilgenfeld R, Jansson A M, Malet H, Mancini E J, Mastrangelo E, Mattevi A, Milani M, Moureau G, Neyts J, Owens R J, Ren J, Selisko B, Speroni S, Steuber H, Stuart D I, Unge T, Bolognesi M (2009a). Structure and functionality in flavivirus NSproteins: Perspectives for drug design. Antiviral Res, 2009 Nov 27. [Epub ahead of print] doi: 10. 1016/j. antiviral. 2009. 11. 009.
  • 18
    • 0019501814 scopus 로고
    • Isolation of a replication-efficient mutant of West Nile virus from a persistently infected genetically resistant mouse cell culture
    • Brinton M A (1981). Isolation of a replication-efficient mutant of West Nile virus from a persistently infected genetically resistant mouse cell culture. J Virol, 39(2): 413-421.
    • (1981) J Virol , vol.39 , Issue.2 , pp. 413-421
    • Brinton, M.A.1
  • 19
    • 0036407156 scopus 로고    scopus 로고
    • The molecular biology of West Nile Virus: a new invader of the western hemisphere
    • Brinton M A (2002). The molecular biology of West Nile Virus: a new invader of the western hemisphere. Annu Rev Microbiol, 56: 371-402.
    • (2002) Annu Rev Microbiol , vol.56 , pp. 371-402
    • Brinton, M.A.1
  • 20
    • 0023853793 scopus 로고
    • Sequence and secondary structure analysis of the 5′-terminal region of flavivirus genome RNA
    • Brinton M A, Dispoto J H (1988). Sequence and secondary structure analysis of the 5′-terminal region of flavivirus genome RNA. Virology, 162(2): 290-299.
    • (1988) Virology , vol.162 , Issue.2 , pp. 290-299
    • Brinton, M.A.1    Dispoto, J.H.2
  • 21
    • 0011094020 scopus 로고    scopus 로고
    • Philadelphia, PA: Lippincott William & Wilkins
    • Burke D S, Monath T P (2001). Flaviviruses. Philadelphia, PA: Lippincott William & Wilkins.
    • (2001) Flaviviruses
    • Burke, D.S.1    Monath, T.P.2
  • 22
    • 0041030653 scopus 로고    scopus 로고
    • Guidelines for surveillance, prevention, and control of West Nile virus infection-United States
    • Centers for Disease ControlPrevention
    • Centers for Disease Control and Prevention (CDC) (2000). Guidelines for surveillance, prevention, and control of West Nile virus infection-United States. MMWR Morb Mortal Wkly Rep, 49(2): 25-28.
    • (2000) MMWR Morb Mortal Wkly Rep , vol.49 , Issue.2 , pp. 25-28
  • 23
  • 24
    • 0026039916 scopus 로고
    • Processing of the yellow fever virus nonstructural polyprotein: a catalytically active NS3 proteinase domain and NS2B are required for cleavages at dibasic sites
    • Chambers T J, Grakoui A, Rice C M (1991). Processing of the yellow fever virus nonstructural polyprotein: a catalytically active NS3 proteinase domain and NS2B are required for cleavages at dibasic sites. J Virol, 65(11): 6042-6050.
    • (1991) J Virol , vol.65 , Issue.11 , pp. 6042-6050
    • Chambers, T.J.1    Grakoui, A.2    Rice, C.M.3
  • 25
    • 0027486484 scopus 로고
    • Mutagenesis of the yellow fever virus NS2B protein: effects on proteolytic processing, NS2B-NS3 complex formation, and viral replication
    • Chambers T J, Nestorowicz A, Amberg S M, Rice C M (1993). Mutagenesis of the yellow fever virus NS2B protein: effects on proteolytic processing, NS2B-NS3 complex formation, and viral replication. J Virol, 67(11): 6797-6807.
    • (1993) J Virol , vol.67 , Issue.11 , pp. 6797-6807
    • Chambers, T.J.1    Nestorowicz, A.2    Amberg, S.M.3    Rice, C.M.4
  • 26
    • 77952571994 scopus 로고    scopus 로고
    • Higher catalytic efficiency of N-7-methylation is responsible for processive N-7 and 2′-O methyltransferase activity in dengue virus
    • Chung K Y, Dong H, Chao A T, Shi P Y, Lescar J, Lim S P (2010). Higher catalytic efficiency of N-7-methylation is responsible for processive N-7 and 2′-O methyltransferase activity in dengue virus. Virology, 402(1): 52-60.
    • (2010) Virology , vol.402 , Issue.1 , pp. 52-60
    • Chung, K.Y.1    Dong, H.2    Chao, A.T.3    Shi, P.Y.4    Lescar, J.5    Lim, S.P.6
  • 27
    • 0018770470 scopus 로고
    • Methylation status of intracellular dengue type 2 40 S RNA
    • Cleaves G R, Dubin D T (1979). Methylation status of intracellular dengue type 2 40 S RNA. Virology, 96(1): 159-165.
    • (1979) Virology , vol.96 , Issue.1 , pp. 159-165
    • Cleaves, G.R.1    Dubin, D.T.2
  • 28
    • 0026759583 scopus 로고
    • Methyltransferase and subunit association domains of vaccinia virus mRNA capping enzyme
    • Cong P, Shuman S (1992). Methyltransferase and subunit association domains of vaccinia virus mRNA capping enzyme. J Biol Chem, 267(23): 16424-16429.
    • (1992) J Biol Chem , vol.267 , Issue.23 , pp. 16424-16429
    • Cong, P.1    Shuman, S.2
  • 29
    • 68649103985 scopus 로고    scopus 로고
    • Chapter 2. New insights into flavivirus nonstructural protein 5
    • Davidson A D (2009). Chapter 2. New insights into flavivirus nonstructural protein 5. Adv Virus Res, 74: 41-101.
    • (2009) Adv Virus Res , vol.74 , pp. 41-101
    • Davidson, A.D.1
  • 30
    • 36549088581 scopus 로고    scopus 로고
    • Structural insights into the mechanism and evolution of the vaccinia virus mRNA cap N7 methyl-transferase
    • De la Peña M, Kyrieleis O J, Cusack S (2007). Structural insights into the mechanism and evolution of the vaccinia virus mRNA cap N7 methyl-transferase. EMBO J, 26(23): 4913-4925.
    • (2007) EMBO J , vol.26 , Issue.23 , pp. 4913-4925
    • de la Peña, M.1    Kyrieleis, O.J.2    Cusack, S.3
  • 31
    • 0033881444 scopus 로고    scopus 로고
    • Infection of human cells by dengue virus is modulated by different cell types and viral strains
    • Diamond M S, Edgil D, Roberts T G, Lu B, Harris E (2000). Infection of human cells by dengue virus is modulated by different cell types and viral strains. J Virol, 74(17): 7814-7823.
    • (2000) J Virol , vol.74 , Issue.17 , pp. 7814-7823
    • Diamond, M.S.1    Edgil, D.2    Roberts, T.G.3    Lu, B.4    Harris, E.5
  • 33
    • 44949192688 scopus 로고    scopus 로고
    • Separate molecules of West Nile virus methyltransferase can independently catalyze the N7 and 2′-O methylations of viral RNA cap
    • Dong H, Ren S, Li H, Shi P Y (2008a). Separate molecules of West Nile virus methyltransferase can independently catalyze the N7 and 2′-O methylations of viral RNA cap. Virology, 377(1): 1-6.
    • (2008) Virology , vol.377 , Issue.1 , pp. 1-6
    • Dong, H.1    Ren, S.2    Li, H.3    Shi, P.Y.4
  • 34
    • 42449160175 scopus 로고    scopus 로고
    • West Nile virus methyltransferase catalyzes two methylations of the viral RNA cap through a substrate-repositioning mechanism
    • Dong H, Ren S, Zhang B, Zhou Y, Puig-Basagoiti F, Li H, Shi P Y (2008b). West Nile virus methyltransferase catalyzes two methylations of the viral RNA cap through a substrate-repositioning mechanism. J Virol, 82(9): 4295-4307.
    • (2008) J Virol , vol.82 , Issue.9 , pp. 4295-4307
    • Dong, H.1    Ren, S.2    Zhang, B.3    Zhou, Y.4    Puig-Basagoiti, F.5    Li, H.6    Shi, P.Y.7
  • 35
    • 50049109958 scopus 로고    scopus 로고
    • Flavivirus methyltransferase: a novel antiviral target
    • Dong H, Zhang B, Shi P Y (2008c). Flavivirus methyltransferase: a novel antiviral target. Antiviral Res, 80(1): 1-10.
    • (2008) Antiviral Res , vol.80 , Issue.1 , pp. 1-10
    • Dong, H.1    Zhang, B.2    Shi, P.Y.3
  • 36
    • 0037013858 scopus 로고    scopus 로고
    • An RNA cap (nucleoside-2′-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization
    • Egloff M P, Benarroch D, Selisko B, Romette J L, Canard B (2002). An RNA cap (nucleoside-2′-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization. EMBO J, 21(11): 2757-2768.
    • (2002) EMBO J , vol.21 , Issue.11 , pp. 2757-2768
    • Egloff, M.P.1    Benarroch, D.2    Selisko, B.3    Romette, J.L.4    Canard, B.5
  • 37
    • 34548148632 scopus 로고    scopus 로고
    • Structural and functional analysis of methylation and 5′-RNA sequence requirements of short capped RNAs by the methyltransferase domain of dengue virus NS5
    • Egloff M P, Decroly E, Malet H, Selisko B, Benarroch D, Ferron F, Canard B (2007). Structural and functional analysis of methylation and 5′-RNA sequence requirements of short capped RNAs by the methyltransferase domain of dengue virus NS5. J Mol Biol, 372(3): 723-736.
    • (2007) J Mol Biol , vol.372 , Issue.3 , pp. 723-736
    • Egloff, M.P.1    Decroly, E.2    Malet, H.3    Selisko, B.4    Benarroch, D.5    Ferron, F.6    Canard, B.7
  • 38
    • 1642482865 scopus 로고    scopus 로고
    • Structure and mechanism of mRNA cap (guanine-N7) methyltransferase
    • Fabrega C, Hausmann S, Shen V, Shuman S, Lima C D (2004). Structure and mechanism of mRNA cap (guanine-N7) methyltransferase. Mol Cell, 13(1): 77-89.
    • (2004) Mol Cell , vol.13 , Issue.1 , pp. 77-89
    • Fabrega, C.1    Hausmann, S.2    Shen, V.3    Shuman, S.4    Lima, C.D.5
  • 39
    • 0027499688 scopus 로고
    • Deletion analysis of dengue virus type 4 nonstructural protein NS2B: identification of a domain required for NS2B-NS3 protease activity
    • Falgout B, Miller R H, Lai C J (1993). Deletion analysis of dengue virus type 4 nonstructural protein NS2B: identification of a domain required for NS2B-NS3 protease activity. J Virol, 67(4): 2034-2042.
    • (1993) J Virol , vol.67 , Issue.4 , pp. 2034-2042
    • Falgout, B.1    Miller, R.H.2    Lai, C.J.3
  • 41
    • 33644752821 scopus 로고    scopus 로고
    • West Nile virus evades activation of interferon regulatory factor 3 through RIG-I-dependent and -independent pathways without antagonizing host defense signaling
    • Fredericksen B L, Gale M Jr (2006). West Nile virus evades activation of interferon regulatory factor 3 through RIG-I-dependent and -independent pathways without antagonizing host defense signaling. J Virol, 80(6): 2913-2923.
    • (2006) J Virol , vol.80 , Issue.6 , pp. 2913-2923
    • Fredericksen, B.L.1    Gale Jr., M.2
  • 42
    • 0015244836 scopus 로고
    • A reporter group at the active site of acetoacetate decarboxylase. I. Ionization constant of the nitrophenol
    • Frey P A, Kokesh F C, Westheimer F H (1971). A reporter group at the active site of acetoacetate decarboxylase. I. Ionization constant of the nitrophenol. J Am Chem Soc, 93(26): 7266-7269.
    • (1971) J Am Chem Soc , vol.93 , Issue.26 , pp. 7266-7269
    • Frey, P.A.1    Kokesh, F.C.2    Westheimer, F.H.3
  • 43
    • 0034567861 scopus 로고    scopus 로고
    • Viral and cellular mRNA capping: past and prospects
    • Furuichi Y, Shatkin A J (2000). Viral and cellular mRNA capping: past and prospects. Adv Virus Res, 55: 135-184.
    • (2000) Adv Virus Res , vol.55 , pp. 135-184
    • Furuichi, Y.1    Shatkin, A.J.2
  • 45
    • 0030612472 scopus 로고    scopus 로고
    • Structure of pvu II DNA-(cytosine N4) methyltransferase, an example of domain permutation and protein fold assignment
    • Gong W, O'Gara M, Blumenthal RM, Cheng X (1997). Structure of pvu II DNA-(cytosine N4) methyltransferase, an example of domain permutation and protein fold assignment. Nucleic Acids Res, 25(14): 2702-2715.
    • (1997) Nucleic Acids Res , vol.25 , Issue.14 , pp. 2702-2715
    • Gong, W.1    O'Gara, M.2    Blumenthal, R.M.3    Cheng, X.4
  • 46
    • 13844256557 scopus 로고    scopus 로고
    • Processing the message: structural insights into capping and decapping mRNA
    • Gu M, Lima C D (2005). Processing the message: structural insights into capping and decapping mRNA. Curr Opin Struct Biol, 15(1): 99-106.
    • (2005) Curr Opin Struct Biol , vol.15 , Issue.1 , pp. 99-106
    • Gu, M.1    Lima, C.D.2
  • 47
    • 0035150449 scopus 로고    scopus 로고
    • Expression and purification of enzymatically active recombinant RNA-dependent RNA polymerase (NS5) of the flavivirus Kunjin
    • Guyatt K J, Westaway E G, Khromykh A A (2001). Expression and purification of enzymatically active recombinant RNA-dependent RNA polymerase (NS5) of the flavivirus Kunjin. J Virol Methods, 92(1): 37-44.
    • (2001) J Virol Methods , vol.92 , Issue.1 , pp. 37-44
    • Guyatt, K.J.1    Westaway, E.G.2    Khromykh, A.A.3
  • 48
    • 0036828880 scopus 로고    scopus 로고
    • Active site in RrmJ, a heat shock-induced methyltransferase
    • Hager J, Staker B L, Bugl H, Jakob U (2002). Active site in RrmJ, a heat shock-induced methyltransferase. J Biol Chem, 277(44): 41978-41986.
    • (2002) J Biol Chem , vol.277 , Issue.44 , pp. 41978-41986
    • Hager, J.1    Staker, B.L.2    Bugl, H.3    Jakob, U.4
  • 49
    • 0030029709 scopus 로고    scopus 로고
    • Mechanism of the reaction catalyzed by acetoacetate decarboxylase. Importance of lysine 116 in determining the pKa of active-site lysine 115
    • Highbarger L A, Gerlt J A, Kenyon G L (1996). Mechanism of the reaction catalyzed by acetoacetate decarboxylase. Importance of lysine 116 in determining the pKa of active-site lysine 115. Biochemistry, 35(1): 41-46.
    • (1996) Biochemistry , vol.35 , Issue.1 , pp. 41-46
    • Highbarger, L.A.1    Gerlt, J.A.2    Kenyon, G.L.3
  • 50
    • 0029665054 scopus 로고    scopus 로고
    • The 1.85 A structure of vaccinia protein VP39: a bifunctional enzyme that participates in the modification of both mRNA ends
    • Hodel A E, Gershon P D, Shi X, Quiocho F A (1996). The 1. 85 A structure of vaccinia protein VP39: a bifunctional enzyme that participates in the modification of both mRNA ends. Cell, 85(2): 247-256.
    • (1996) Cell , vol.85 , Issue.2 , pp. 247-256
    • Hodel, A.E.1    Gershon, P.D.2    Shi, X.3    Quiocho, F.A.4
  • 51
    • 0031993338 scopus 로고    scopus 로고
    • Structural basis for sequence-nonspecific recognition of 5′-capped mRNA by a capmodifying enzyme
    • Hodel A E, Gershon P D, Quiocho F A (1998). Structural basis for sequence-nonspecific recognition of 5′-capped mRNA by a capmodifying enzyme. Mol Cell, 1(3): 443-447.
    • (1998) Mol Cell , vol.1 , Issue.3 , pp. 443-447
    • Hodel, A.E.1    Gershon, P.D.2    Quiocho, F.A.3
  • 52
    • 77956132753 scopus 로고    scopus 로고
    • Hodel A E, Quiocho F A, Gershon P D (1999). VP39-an mRNA capspecific 2′-o-methyltransferase. In: X. D. Cheng and R. M. Blementhal, eds. S-Adenosylmethionine-dependent methyltransferase: structures and functions. 255-282.
  • 54
    • 0034812118 scopus 로고    scopus 로고
    • Two polymorphic forms of human histamine methyltransferase: structural, thermal, and kinetic comparisons
    • Horton J R, Sawada K, Nishibori M, Zhang X, Cheng X (2001). Two polymorphic forms of human histamine methyltransferase: structural, thermal, and kinetic comparisons. Structure, 9(9): 837-849.
    • (2001) Structure , vol.9 , Issue.9 , pp. 837-849
    • Horton, J.R.1    Sawada, K.2    Nishibori, M.3    Zhang, X.4    Cheng, X.5
  • 55
    • 73249127604 scopus 로고    scopus 로고
    • The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure
    • Issur M, Geiss B J, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey S E, Bisaillon M (2009). The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA, 15(12): 2340-2350.
    • (2009) Rna , vol.15 , Issue.12 , pp. 2340-2350
    • Issur, M.1    Geiss, B.J.2    Bougie, I.3    Picard-Jean, F.4    Despins, S.5    Mayette, J.6    Hobdey, S.E.7    Bisaillon, M.8
  • 57
    • 0021770887 scopus 로고
    • Primary structural comparison of RNA-dependent polymerases from plant, animal and bacterial viruses
    • Kamer G, Argos P (1984). Primary structural comparison of RNA-dependent polymerases from plant, animal and bacterial viruses. Nucleic Acids Res, 12(18): 7269-7282.
    • (1984) Nucleic Acids Res , vol.12 , Issue.18 , pp. 7269-7282
    • Kamer, G.1    Argos, P.2
  • 58
    • 0031870247 scopus 로고    scopus 로고
    • Transcomplementation of flavivirus RNA polymerase gene NS5 by using Kunjin virus replicon-expressing BHK cells
    • Khromykh A A, Kenney M T, Westaway E G (1998). Transcomplementation of flavivirus RNA polymerase gene NS5 by using Kunjin virus replicon-expressing BHK cells. J Virol, 72(9): 7270-7279.
    • (1998) J Virol , vol.72 , Issue.9 , pp. 7270-7279
    • Khromykh, A.A.1    Kenney, M.T.2    Westaway, E.G.3
  • 59
    • 0015244831 scopus 로고
    • A reporter group at the active site of acetoacetate decarboxylase. II. Ionization constant of the amino group
    • Kokesh F C, Westheimer F H (1971). A reporter group at the active site of acetoacetate decarboxylase. II. Ionization constant of the amino group. J Am Chem Soc, 93(26): 7270-7274.
    • (1971) J Am Chem Soc , vol.93 , Issue.26 , pp. 7270-7274
    • Kokesh, F.C.1    Westheimer, F.H.2
  • 60
    • 0036298629 scopus 로고    scopus 로고
    • Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase
    • Komoto J, Huang Y, Takata Y, Yamada T, Konishi K, Ogawa H, Gomi T, Fujioka M, Takusagawa F (2002). Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase. J Mol Biol, 320(2): 223-235.
    • (2002) J Mol Biol , vol.320 , Issue.2 , pp. 223-235
    • Komoto, J.1    Huang, Y.2    Takata, Y.3    Yamada, T.4    Konishi, K.5    Ogawa, H.6    Gomi, T.7    Fujioka, M.8    Takusagawa, F.9
  • 61
    • 0025743809 scopus 로고
    • The phylogeny of RNA-dependent RNA polymerases of positive-strand RNA viruses
    • Koonin E V (1991). The phylogeny of RNA-dependent RNA polymerases of positive-strand RNA viruses. J Gen Virol, 72(Pt 9): 2197-2206.
    • (1991) J Gen Virol , vol.72 , Issue.Pt9 , pp. 2197-2206
    • Koonin, E.V.1
  • 62
    • 0027474037 scopus 로고
    • Computer-assisted identification of a putative methyltransferase domain in NS5 protein of flaviviruses and lambda 2 protein of reovirus
    • Koonin E V (1993). Computer-assisted identification of a putative methyltransferase domain in NS5 protein of flaviviruses and lambda 2 protein of reovirus. J Gen Virol, 74(Pt 4): 733-740.
    • (1993) J Gen Virol , vol.74 , Issue.Pt4 , pp. 733-740
    • Koonin, E.V.1
  • 63
    • 0035686797 scopus 로고    scopus 로고
    • West Nile virus infection in birds and mammals
    • Kramer L D, Bernard K A (2001). West Nile virus infection in birds and mammals. Ann N Y Acad Sci, 951: 84-93.
    • (2001) Ann N Y Acad Sci , vol.951 , pp. 84-93
    • Kramer, L.D.1    Bernard, K.A.2
  • 66
    • 0036232747 scopus 로고    scopus 로고
    • Mutations in the yellow fever virus nonstructural protein NS2A selectively block production of infectious particles
    • Kümmerer B M, Rice C M (2002). Mutations in the yellow fever virus nonstructural protein NS2A selectively block production of infectious particles. J Virol, 76(10): 4773-4784.
    • (2002) J Virol , vol.76 , Issue.10 , pp. 4773-4784
    • Kümmerer, B.M.1    Rice, C.M.2
  • 67
    • 0037439085 scopus 로고    scopus 로고
    • Mechanism of histone lysine methyl transfer revealed by the structure of SET7/9-AdoMet
    • Kwon T, Chang J H, Kwak E, Lee C W, Joachimiak A, Kim Y C, Lee J, Cho Y (2003). Mechanism of histone lysine methyl transfer revealed by the structure of SET7/9-AdoMet. EMBO J, 22(2): 292-303.
    • (2003) EMBO J , vol.22 , Issue.2 , pp. 292-303
    • Kwon, T.1    Chang, J.H.2    Kwak, E.3    Lee, C.W.4    Joachimiak, A.5    Kim, Y.C.6    Lee, J.7    Cho, Y.8
  • 68
    • 0032976077 scopus 로고    scopus 로고
    • The serine protease and RNA-stimulated nucleoside triphosphatase and RNA helicase functional domains of dengue virus type 2 NS3 converge within a region of 20 amino acids
    • Li H, Clum S, You S, Ebner K E, Padmanabhan R (1999). The serine protease and RNA-stimulated nucleoside triphosphatase and RNA helicase functional domains of dengue virus type 2 NS3 converge within a region of 20 amino acids. J Virol, 73(4): 3108-3116.
    • (1999) J Virol , vol.73 , Issue.4 , pp. 3108-3116
    • Li, H.1    Clum, S.2    You, S.3    Ebner, K.E.4    Padmanabhan, R.5
  • 69
    • 33744795205 scopus 로고    scopus 로고
    • A unique strategy for mRNA cap methylation used by vesicular stomatitis virus
    • Li J, Wang J T, Whelan S P (2006). A unique strategy for mRNA cap methylation used by vesicular stomatitis virus. Proc Natl Acad Sci U S A, 103(22): 8493-8498.
    • (2006) Proc Natl Acad Sci U S A , vol.103 , Issue.22 , pp. 8493-8498
    • Li, J.1    Wang, J.T.2    Whelan, S.P.3
  • 70
    • 41349112506 scopus 로고    scopus 로고
    • The flavivirus precursor membrane-envelope protein complex: structure and maturation
    • Li L, Lok S M, Yu I M, Zhang Y, Kuhn R J, Chen J, Rossmann M G (2008). The flavivirus precursor membrane-envelope protein complex: structure and maturation. Science, 319(5871): 1830-1834.
    • (2008) Science , vol.319 , Issue.5871 , pp. 1830-1834
    • Li, L.1    Lok, S.M.2    Yu, I.M.3    Zhang, Y.4    Kuhn, R.J.5    Chen, J.6    Rossmann, M.G.7
  • 71
    • 56349149403 scopus 로고    scopus 로고
    • A scintillation proximity assay for dengue virus NS5 2′-O-methyltransferase-kinetic and inhibition analyses
    • Lim S P, Wen D, Yap T L, Yan C K, Lescar J, Vasudevan S G (2008). A scintillation proximity assay for dengue virus NS5 2′-O-methyltransferase-kinetic and inhibition analyses. Antiviral Res, 80(3): 360-369.
    • (2008) Antiviral Res , vol.80 , Issue.3 , pp. 360-369
    • Lim, S.P.1    Wen, D.2    Yap, T.L.3    Yan, C.K.4    Lescar, J.5    Vasudevan, S.G.6
  • 72
    • 0030774240 scopus 로고    scopus 로고
    • Trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication
    • Lindenbach B D, Rice C M (1997). trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol, 71(12): 9608-9617.
    • (1997) J Virol , vol.71 , Issue.12 , pp. 9608-9617
    • Lindenbach, B.D.1    Rice, C.M.2
  • 73
    • 0033034992 scopus 로고    scopus 로고
    • Genetic interaction of flavivirus nonstructural proteins NS1 and NS4A as a determinant of replicase function
    • Lindenbach B D, Rice C M (1999). Genetic interaction of flavivirus nonstructural proteins NS1 and NS4A as a determinant of replicase function. J Virol, 73(6): 4611-4621.
    • (1999) J Virol , vol.73 , Issue.6 , pp. 4611-4621
    • Lindenbach, B.D.1    Rice, C.M.2
  • 75
    • 0028841409 scopus 로고
    • Structure-guided analysis reveals nine sequence motifs conserved among DNA amino-methyltransferases, and suggests a catalytic mechanism for these enzymes
    • Malone T, Blumenthal R M, Cheng X (1995). Structure-guided analysis reveals nine sequence motifs conserved among DNA amino-methyltransferases, and suggests a catalytic mechanism for these enzymes. J Mol Biol, 253(4): 618-632.
    • (1995) J Mol Biol , vol.253 , Issue.4 , pp. 618-632
    • Malone, T.1    Blumenthal, R.M.2    Cheng, X.3
  • 76
    • 0036917889 scopus 로고    scopus 로고
    • SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold
    • Martin J L, McMillan F M (2002). SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold. Curr Opin Struct Biol, 12(6): 783-793.
    • (2002) Curr Opin Struct Biol , vol.12 , Issue.6 , pp. 783-793
    • Martin, J.L.1    McMillan, F.M.2
  • 79
    • 33646164166 scopus 로고    scopus 로고
    • Crystal structures of the vaccinia virus polyadenylate polymerase heterodimer: insights into ATP selectivity and processivity
    • Moure C M, Bowman B R, Gershon P D, Quiocho F A (2006). Crystal structures of the vaccinia virus polyadenylate polymerase heterodimer: insights into ATP selectivity and processivity. Mol Cell, 22(3): 339-349.
    • (2006) Mol Cell , vol.22 , Issue.3 , pp. 339-349
    • Moure, C.M.1    Bowman, B.R.2    Gershon, P.D.3    Quiocho, F.A.4
  • 80
    • 0030218225 scopus 로고    scopus 로고
    • Mutagenesis of the N-linked glycosylation sites of the yellow fever virus NS1 protein: effects on virus replication and mouse neurovirulence
    • Muylaert I R, Chambers T J, Galler R, Rice C M (1996). Mutagenesis of the N-linked glycosylation sites of the yellow fever virus NS1 protein: effects on virus replication and mouse neurovirulence. Virology, 222(1): 159-168.
    • (1996) Virology , vol.222 , Issue.1 , pp. 159-168
    • Muylaert, I.R.1    Chambers, T.J.2    Galler, R.3    Rice, C.M.4
  • 81
    • 0031060332 scopus 로고    scopus 로고
    • Genetic analysis of the yellow fever virus NS1 protein: identification of a temperature-sensitive mutation which blocks RNA accumulation
    • Muylaert I R, Galler R, Rice C M (1997). Genetic analysis of the yellow fever virus NS1 protein: identification of a temperature-sensitive mutation which blocks RNA accumulation. J Virol, 71(1): 291-298.
    • (1997) J Virol , vol.71 , Issue.1 , pp. 291-298
    • Muylaert, I.R.1    Galler, R.2    Rice, C.M.3
  • 82
    • 0026319199 scopus 로고
    • Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons
    • Nicholls A, Sharp K A, Honig B (1991). Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins, 11(4): 281-296.
    • (1991) Proteins , vol.11 , Issue.4 , pp. 281-296
    • Nicholls, A.1    Sharp, K.A.2    Honig, B.3
  • 83
    • 33845992557 scopus 로고    scopus 로고
    • Unconventional mechanism of mRNA capping by the RNA-dependent RNA polymerase of vesicular stomatitis virus
    • Ogino T, Banerjee A K (2007). Unconventional mechanism of mRNA capping by the RNA-dependent RNA polymerase of vesicular stomatitis virus. Mol Cell, 25(1): 85-97.
    • (2007) Mol Cell , vol.25 , Issue.1 , pp. 85-97
    • Ogino, T.1    Banerjee, A.K.2
  • 84
    • 48749123790 scopus 로고    scopus 로고
    • Structural proteomics of dengue virus
    • Perera R, Kuhn R J (2008). Structural proteomics of dengue virus. Curr Opin Microbiol, 11(4): 369-377.
    • (2008) Curr Opin Microbiol , vol.11 , Issue.4 , pp. 369-377
    • Perera, R.1    Kuhn, R.J.2
  • 85
    • 0034852978 scopus 로고    scopus 로고
    • West Nile virus: a reemerging global pathogen
    • Petersen L R, Roehrig J T (2001). West Nile virus: a reemerging global pathogen. Emerg Infect Dis, 7(4): 611-614.
    • (2001) Emerg Infect Dis , vol.7 , Issue.4 , pp. 611-614
    • Petersen, L.R.1    Roehrig, J.T.2
  • 86
    • 34047219728 scopus 로고    scopus 로고
    • High-yield production of short GpppA- and 7MeGpppA-capped RNAs and HPLC-monitoring of methyltransfer reactions at the guanine-N7 and adenosine-2′O positions
    • Peyrane F, Selisko B, Decroly E, Vasseur J J, Benarroch D, Canard B, Alvarez K (2007). High-yield production of short GpppA- and 7MeGpppA-capped RNAs and HPLC-monitoring of methyltransfer reactions at the guanine-N7 and adenosine-2′O positions. Nucleic Acids Res, 35(4): e26.
    • (2007) Nucleic Acids Res , vol.35 , Issue.4
    • Peyrane, F.1    Selisko, B.2    Decroly, E.3    Vasseur, J.J.4    Benarroch, D.5    Canard, B.6    Alvarez, K.7
  • 87
    • 77649229290 scopus 로고    scopus 로고
    • Novel inhibitors of dengue virus methyltransferase: discovery by in vitro-driven virtual screening on a desktop computer grid
    • Podvinec M, Lim S P, Schmidt T, Scarsi M, Wen D, Sonntag L S, Sanschagrin P, Shenkin P S, Schwede T (2010). Novel inhibitors of dengue virus methyltransferase: discovery by in vitro-driven virtual screening on a desktop computer grid. JMed Chem, 53(4): 1483-1495.
    • (2010) JMed Chem , vol.53 , Issue.4 , pp. 1483-1495
    • Podvinec, M.1    Lim, S.P.2    Schmidt, T.3    Scarsi, M.4    Wen, D.5    Sonntag, L.S.6    Sanschagrin, P.7    Shenkin, P.S.8    Schwede, T.9
  • 89
    • 33748669852 scopus 로고    scopus 로고
    • West Nile virus 5′-cap structure is formed by sequential guanine N-7 and ribose 2′-O methylations by nonstructural protein 5
    • Ray D, Shah A, Tilgner M, Guo Y, Zhao Y, Dong H, Deas T S, Zhou Y, Li H, Shi P Y (2006). West Nile virus 5′-cap structure is formed by sequential guanine N-7 and ribose 2′-O methylations by nonstructural protein 5. J Virol, 80(17): 8362-8370.
    • (2006) J Virol , vol.80 , Issue.17 , pp. 8362-8370
    • Ray, D.1    Shah, A.2    Tilgner, M.3    Guo, Y.4    Zhao, Y.5    Dong, H.6    Deas, T.S.7    Zhou, Y.8    Li, H.9    Shi, P.Y.10
  • 90
    • 0034720237 scopus 로고    scopus 로고
    • Structure of the reovirus core at 3.6 A resolution
    • Reinisch K M, Nibert M L, Harrison S C (2000). Structure of the reovirus core at 3. 6 A resolution. Nature, 404(6781): 960-967.
    • (2000) Nature , vol.404 , Issue.6781 , pp. 960-967
    • Reinisch, K.M.1    Nibert, M.L.2    Harrison, S.C.3
  • 91
    • 0021863828 scopus 로고
    • Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution
    • Rice C M, Lenches E M, Eddy S R, Shin S J, Sheets R L, Strauss J H (1985). Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. Science, 229(4715): 726-733.
    • (1985) Science , vol.229 , Issue.4715 , pp. 726-733
    • Rice, C.M.1    Lenches, E.M.2    Eddy, S.R.3    Shin, S.J.4    Sheets, R.L.5    Strauss, J.H.6
  • 92
    • 57149088067 scopus 로고    scopus 로고
    • Molecular targets for flavivirus drug discovery
    • Sampath A, Padmanabhan R (2009). Molecular targets for flavivirus drug discovery. Antiviral Res, 81(1): 6-15.
    • (2009) Antiviral Res , vol.81 , Issue.1 , pp. 6-15
    • Sampath, A.1    Padmanabhan, R.2
  • 93
    • 0028109273 scopus 로고
    • Mutational analysis of a multifunctional protein, with mRNA 5′ cap-specific (nucleoside-2′-O-)-methyltransferase and 3′-adenylyltransferase stimulatory activities, encoded by vaccinia virus
    • Schnierle B S, Gershon P D, Moss B (1994). Mutational analysis of a multifunctional protein, with mRNA 5′ cap-specific (nucleoside-2′-O-)-methyltransferase and 3′-adenylyltransferase stimulatory activities, encoded by vaccinia virus. J Biol Chem, 269(32): 20700-20706.
    • (1994) J Biol Chem , vol.269 , Issue.32 , pp. 20700-20706
    • Schnierle, B.S.1    Gershon, P.D.2    Moss, B.3
  • 94
    • 73149108394 scopus 로고    scopus 로고
    • Biochemical characterization of the (nucleoside-2′O)-methyltransferase activity of dengue virus protein NS5 using purified capped RNA oligonucleotides (7Me)GpppAC(n) and GpppAC(n)
    • Selisko B, Peyrane F F, Canard B, Alvarez K, Decroly E (2010). Biochemical characterization of the (nucleoside-2′O)-methyltransferase activity of dengue virus protein NS5 using purified capped RNA oligonucleotides (7Me)GpppAC(n) and GpppAC(n). J Gen Virol, 91(Pt 1): 112-121.
    • (2010) J Gen Virol , vol.91 , Issue.Pt1 , pp. 112-121
    • Selisko, B.1    Peyrane, F.F.2    Canard, B.3    Alvarez, K.4    Decroly, E.5
  • 96
    • 0036298395 scopus 로고    scopus 로고
    • Construction and characterization of subgenomic replicons of New York strain of West Nile virus
    • Shi P Y, Tilgner M, Lo M K (2002a). Construction and characterization of subgenomic replicons of New York strain of West Nile virus. Virology, 296(2): 219-233.
    • (2002) Virology , vol.296 , Issue.2 , pp. 219-233
    • Shi, P.Y.1    Tilgner, M.2    Lo, M.K.3
  • 97
    • 0036107695 scopus 로고    scopus 로고
    • Infectious cDNA clone of the epidemic west nile virus from New York City
    • Shi P Y, Tilgner M, Lo MK, Kent K A, Bernard K A (2002b). Infectious cDNA clone of the epidemic west nile virus from New York City. J Virol, 76(12): 5847-5856.
    • (2002) J Virol , vol.76 , Issue.12 , pp. 5847-5856
    • Shi, P.Y.1    Tilgner, M.2    Lo, M.K.3    Kent, K.A.4    Bernard, K.A.5
  • 99
    • 0035201941 scopus 로고    scopus 로고
    • Structure, mechanism, and evolution of the mRNA capping apparatus
    • Shuman S (2001). Structure, mechanism, and evolution of the mRNA capping apparatus. Prog Nucleic Acid Res Mol Biol, 66: 1-40.
    • (2001) Prog Nucleic Acid Res Mol Biol , vol.66 , pp. 1-40
    • Shuman, S.1
  • 101
    • 34247570020 scopus 로고    scopus 로고
    • Bluetongue virus VP4 is an RNA-capping assembly line
    • Sutton G, Grimes JM, Stuart D I, Roy P (2007). Bluetongue virus VP4 is an RNA-capping assembly line. Nat Struct Mol Biol, 14(5): 449-451.
    • (2007) Nat Struct Mol Biol , vol.14 , Issue.5 , pp. 449-451
    • Sutton, G.1    Grimes, J.M.2    Stuart, D.I.3    Roy, P.4
  • 102
    • 0029863798 scopus 로고    scopus 로고
    • Recombinant dengue type 1 virus NS5 protein expressed in Escherichia coli exhibits RNA-dependent RNA polymerase activity
    • Tan B H, Fu J, Sugrue R J, Yap E H, Chan Y C, Tan Y H (1996). Recombinant dengue type 1 virus NS5 protein expressed in Escherichia coli exhibits RNA-dependent RNA polymerase activity. Virology, 216(2): 317-325.
    • (1996) Virology , vol.216 , Issue.2 , pp. 317-325
    • Tan, B.H.1    Fu, J.2    Sugrue, R.J.3    Yap, E.H.4    Chan, Y.C.5    Tan, Y.H.6
  • 103
    • 0027446550 scopus 로고
    • RNA-stimulated NTPase activity associated with yellow fever virus NS3 protein expressed in bacteria
    • Warrener P, Tamura J K, Collett M S (1993). RNA-stimulated NTPase activity associated with yellow fever virus NS3 protein expressed in bacteria. J Virol, 67(2): 989-996.
    • (1993) J Virol , vol.67 , Issue.2 , pp. 989-996
    • Warrener, P.1    Tamura, J.K.2    Collett, M.S.3
  • 104
    • 0019418822 scopus 로고
    • Terminal sequences of the genome and replicative-from RNA of the flavivirus West Nile virus: absence of poly(A) and possible role in RNA replication
    • Wengler G, Wengler G (1981). Terminal sequences of the genome and replicative-from RNA of the flavivirus West Nile virus: absence of poly(A) and possible role in RNA replication. Virology, 113(2): 544-555.
    • (1981) Virology , vol.113 , Issue.2 , pp. 544-555
    • Wengler, G.1    Wengler, G.2
  • 105
    • 0025945616 scopus 로고
    • The carboxy-terminal part of the NS 3 protein of theWest Nile flavivirus can be isolated as a soluble protein after proteolytic cleavage and represents an RNA-stimulated NTPase
    • Wengler G, Wengler G (1991). The carboxy-terminal part of the NS 3 protein of theWest Nile flavivirus can be isolated as a soluble protein after proteolytic cleavage and represents an RNA-stimulated NTPase. Virology, 184(2): 707-715.
    • (1991) Virology , vol.184 , Issue.2 , pp. 707-715
    • Wengler, G.1    Wengler, G.2
  • 107
    • 11144335196 scopus 로고    scopus 로고
    • WHO
    • WHO (2009a). Dengue factsheet. http://www. who. int/mediacentre/factsheets/fs117/en/.
    • (2009) Dengue factsheet
  • 109
    • 77956130081 scopus 로고    scopus 로고
    • WHO
    • WHO (2009c). Yellow fever factsheet. http://www. who. int/mediacentre/factsheets/fs100/en/.
    • (2009) Yellow fever factsheet
  • 111
    • 0034679591 scopus 로고    scopus 로고
    • Crystal structure of the conserved core of protein arginine methyltransferase PRMT3
    • Zhang X, Zhou L, Cheng X (2000). Crystal structure of the conserved core of protein arginine methyltransferase PRMT3. EMBO J, 19(14): 3509-3519.
    • (2000) EMBO J , vol.19 , Issue.14 , pp. 3509-3519
    • Zhang, X.1    Zhou, L.2    Cheng, X.3
  • 113
    • 0035119588 scopus 로고    scopus 로고
    • Structures of two natural product methyltransferases reveal the basis for substrate specificity in plant O-methyltransferases
    • Zubieta C, He X Z, Dixon R A, Noel J P (2001). Structures of two natural product methyltransferases reveal the basis for substrate specificity in plant O-methyltransferases. Nat Struct Biol, 8(3): 271-279.
    • (2001) Nat Struct Biol , vol.8 , Issue.3 , pp. 271-279
    • Zubieta, C.1    He, X.Z.2    Dixon, R.A.3    Noel, J.P.4
  • 114
    • 0042121256 scopus 로고    scopus 로고
    • Mfold web server for nucleic acid folding and hybridization prediction
    • Zuker M (2003). Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res, 31(13): 3406-3415.
    • (2003) Nucleic Acids Res , vol.31 , Issue.13 , pp. 3406-3415
    • Zuker, M.1


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.