Two-metal ion mechanism of RNA cleavage by HIV RNase H and mechanism-based design of selective HIV RNase H inhibitors

Nucleic Acids Research

Volumn 31, Issue 23, 2003, Pages 6852-6859

  Klumpp, Klaus ^a,b   Hang, Julie Qi ^b   Rajendran, Surendran ^b   Yang, Yanli ^b   Derosier, Andre ^b   Kai In, Philippe Wong ^a,c   Overton, Hilary ^a,c   Parkes, Kevin E B ^a,b,d   Cammack, Nick ^a,b   Martin, Joseph A ^a,b  

^a ROCHE PRODUCTS LTD   (United Kingdom)

^b ROCHE BIOSCIENCE   (United States)

^c OSI Pharmaceuticals   (United Kingdom)

^d MEDIVIR AB   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

COBALT; DIVALENT CATION; ENZYME INHIBITOR; IMIDE; MAGNESIUM ION; MANGANESE; METAL ION; NUCLEASE; RIBONUCLEASE H; RNA DIRECTED DNA POLYMERASE; RNA POLYMERASE; VIRUS DNA; VIRUS ENZYME;

ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DNA SYNTHESIS; DRUG DESIGN; DRUG IDENTIFICATION; DRUG POTENCY; DRUG SELECTIVITY; ENZYME ACTIVATION; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME BINDING; ENZYME INHIBITION; ENZYME MECHANISM; ENZYME STRUCTURE; ESCHERICHIA COLI; HUMAN IMMUNODEFICIENCY VIRUS; IC 50; MEASUREMENT; METAL BINDING; MOLECULAR MECHANICS; MOLECULAR SIZE; NONHUMAN; PRIORITY JOURNAL; PROBABILITY; RNA CLEAVAGE; STRUCTURAL HOMOLOGY; STRUCTURE ACTIVITY RELATION; TITRIMETRY;

BINDING SITES; CATIONS, DIVALENT; DRUG DESIGN; ENZYME ACTIVATION; ENZYME INHIBITORS; ESCHERICHIA COLI; HIV; METALS; RIBONUCLEASE H, CALF THYMUS; SUBSTRATE SPECIFICITY;

DNA VIRUSES; ESCHERICHIA COLI; HUMAN IMMUNODEFICIENCY VIRUS; RNA VIRUSES;

EID: 10744226166     PISSN: 03051048     EISSN: None     Source Type: Journal    
DOI: 10.1093/nar/gkg881     Document Type: Article

References (37)

1. Freed,E.O. and Martin,M.A. (2001) HIVs and their replication. In Knipe,D. and Howley,P. (eds), Fields Virology. Lippincott Williams & Wilkins, Philadelphia, PA, Vol. 2, pp. 1971-2042.
2. Telesnitsky,A. and Goff,S.P. (1997) Reverse transcription and the generation of retroviral DNA. In Coffin,J.M., Hughes,S.H. and Varmus,H.E. (eds), Retroviruses. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 121-160.
3. Schatz,O., Cromme,F.V., Nass,T. and Lindemann,D. (1989) Inactivation of RNaseH domain of HIV-1 reverse transcriptase blocks viral infectivity. In Papas,T.S. (ed.), Gene Regulation and AIDS: Transcriptional Activation, Retroviruses and Pathogenesis. Gulf Publishing Company, Houston, TX, pp. 293-303.
4. Tisdale,M., Schulze,T., Larder,B.A. and Moelling,K. (1991) Mutations within the RNase H domain of human immunodeficiency virus type 1 reverse transcriptase abolish virus infectivity. J. Gen. Viral., 72, 59-66.
5. Andreola,M.L., De Soultrait,V.R., Fournier,M., Parissi,V., Desjobert,C. and Litvak,S. (2002) HIV-1 integrase and RNase H activities as therapeutic targets. Expert Opin. Ther. Targets, 6, 433-446.
6. Shaw-Reid,C.A., Munshi,V., Graham,P., Wolfe,A., Witmer,M., Danzeisen,R., Olsen,D.B., Carroll,S.S., Embrey,M., Wai,J.S., Miller,M.D., Cole,J.L. and Hazuda,D.J. (2003) Inhibition of HIV-1 ribonuclease H by a novel diketo acid, 4-[5-(benzoylamino)thien-2-yl]-2,4-dioxobutanoic acid. J. Biol. Chem., 278, 2777-2780.
7. Tomassini,J., Selnick,H., Davies,M.E., Armstrong,M.E., Baldwin,J., Bourgeois,M., Hastings,J., Hazuda,D., Lewis,J., McClements,W., Ponticello,G., Radzilowski,E., Smith,G., Tebben,A. and Wolfe,A. (1994) Inhibition of cap (m7GpppXm)-dependent endonuclease of influenza virus by 4-substituted 2,4-dioxobutanoic acid compounds. Antimicrob. Agents Chemother., 38, 2827-2837.
8. Hastings,J.C., Selnick,H., Wolanski,B. and Tomassini,J.E. (1996) Anti-influenza virus activities of 4-substituted 2,4-dioxobutanoic acid inhibitors. Antimicrob. Agents Chemother., 40, 1304-1307.
9. Doan,L., Handa,B., Roberts,N.A. and Klumpp,K. (1999) Metal ion catalysis of RNA cleavage by the influenza virus endonuclease. Biochemistry, 38, 5612-5619.
10. Beese,L.S. and Steitz,T.A. (1991) Structural basis for the 3′-5′ exonuclease activity of Escherichia coli DNA polymerase I: a two metal ion mechanism. EMBO J., 10, 25-33.
11. Parkes,K.E., Ermert,P., Fassler,J., Ives,J., Martin,J.A., Merrett,J.H., Obrecht,D., Williams,G. and Klumpp,K. (2003) Use of a pharmacophore model to discover a new class of influenza endonuclease inhibitors. J. Med. Chem., 46, 1153-1164.
12. Davies,J.F.,II, Hostomska,Z., Hostomsky,Z., Jordan,S.R. and Matthews,D.A. (1991) Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase. Science, 252, 88-95.
13. Cowan,J.A., Ohyama,T., Howard,K., Rausch,J.W., Cowan,S.M. and Le Grice,S.F. (2000) Metal-ion stoichiometry of the HIV-1 RT ribonuclease H domain: evidence for two mutually exclusive sites leads to new mechanistic insights on metal-mediated hydrolysis in nucleic acid biochemistry. J. Biol. Inorg. Chem., 5, 67-74.
14. Cristofaro,J.V., Rausch,J.W., Le Grice,S.F. and DeStefano,J.J. (2002) Mutations in the ribonuclease H active site of HIV-RT reveal a role for this site in stabilizing enzyme-primer-template binding. Biochemistry, 41, 10968-10975.
15. Pari,K., Mueller,G.A., DeRose,E.F., Kirby,T.W. and London,R.E. (2003) Solution structure of the RNase H domain of the HIV-1 reverse transcriptase in the presence of magnesium. Biochemistry, 42, 639-650.
16. 2+ ion. Proposal of a novel catalytic role for Glu48. J. Biol. Chem., 271, 32729-32736.
17. Haruki,M., Tsunaka,Y., Morikawa,M., Iwai,S. and Kanaya,S. (2000) Catalysis by Escherichia coli ribonuclease HI is facilitated by a phosphate group of the substrate. Biochemistry, 39, 13939-13944.
18. 2+ at 2.8 Å resolution: proof for a single Mg(2+)-binding site. Proteins, 17, 337-346.
19. 15N heteronuclear 2D NMR. J. Biomol. NMR, 1, 247-255.
20. Huang,H.W. and Cowan,J.A. (1994) Metallobiochemistry of the magnesium ion. Characterization of the essential metal-binding site in Escherichia coli ribonuclease H. Eur. J. Biochem., 219, 253-260.
21. 2+ ions reveals two divalent metals bound in the active site. J. Biol. Chem., 276, 7266-7271.
22. Keck,J.L., Goedken,E.R. and Marqusee,S. (1998) Activation/attenuation model for RNase H. A one-metal mechanism with second-metal inhibition. J. Biol. Chem., 273, 34128-34133.
23. Goedken,E.R., Keck,J.L., Berger,J.M. and Marqusee,S. (2000) Divalent metal cofactor binding in the kinetic folding trajectory of Escherichia coli ribonuclease HI. Protein Sci., 9, 1914-1921.
24. LeGrice,S.F. and Gruninger-Leitch,F. (1990) Rapid purification of homodimer and heterodimer HIV-1 reverse transcriptase by metal chelate affinity chromatography. Eur. J. Biochem., 187, 307-314.
25. Klumpp,K., Hooker,L. and Handa,B. (2001) Influenza virus endoribonuclease. Methods Enzymol., 342, 451-466.
26. Sarafianos,S.G., Das,K., Tantillo,C., Clark,A.D.,Jr, Ding,J., Whitcomb,J.M., Boyer,P.L., Hughes,S.H. and Arnold,E. (2001) Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA. EMBO J., 20, 1449-1461.
27. Schatz,O., Mous,J. and Le Grice,S.F. (1990) HIV-1 RT-associated ribonuclease H displays both endonuclease and 3′-5′ exonuclease activity. EMBO J., 9, 1171-1176.
28. Wohrl,B.M. and Moelling,K. (1990) Interaction of HIV-1 fibonuclease H with polypurine tract containing RNA-DNA hybrids. Biochemistry, 29, 10141-10147.
29. Gopalakrishnan,V., Peliska,J.A. and Benkovic,S.J. (1992) Human immunodeficiency virus type 1 reverse transcriptase: spatial and temporal relationship between the polymerase and RNase H activities. Proc. Natl Acad. Sci. USA, 89, 10763-10767.
30. Gotte,M., Maier,G., Gross,H.J. and Heumann,H. (1998) Localization of the active site of HIV-1 reverse transcriptase-associated RNase H domain on a DNA template using site-specific generated hydroxyl radicals. J. Biol. Chem., 273, 10139-10146.
31. Palaniappan,C., Fuentes,G.M., Rodriguez-Rodriguez,L., Fay,P.J. and Bambara,R.A. (1996) Helix structure and ends of RNA-DNA hybrids direct the cleavage specificity of HIV-1 reverse transcriptase RNase H. J. Biol. Chem., 271, 2063-2070.
32. Wisniewski,M., Balakrishnan,M., Palaniappan,C., Fay,P.J. and Bambara,R.A. (2000) Unique progressive cleavage mechanism of HIV reverse transcriptase RNase H. Proc. Natl Acad. Sci. USA, 97, 11978-11983.
33. Wisniewski,M., Chen,Y., Balakrishnan,M., Palaniappan,C., Roques,B.P., Fay,P.J. and Bambara,R.A. (2002) Substrate requirements for secondary cleavage by HIV-1 reverse transcriptase RNase H. J. Biol. Chem., 277, 28400-28410.
34. Lott,W.B., Pontius,B.W. and von Hippel,P.H. (1998) A two-metal ion mechanism operates in the hammerhead ribozyme-mediated cleavage of an RNA substrate. Proc. Natl Acad. Sci. USA, 95, 542-547.
35. Li,Y., Korolev,S. and Waksman,G. (1998) Crystal structures of open and closed forms of binary and ternary complexes of the large fragment of Thermus aquaticus DNA polymerase I: structural basis for nucleotide incorporation. EMBO J., 17, 7514-7525.
36. Steitz,T.A. (1998) A mechanism for all polymerases. Nature, 391, 231-232.
37. Sosunov,V., Sosunova,E., Mustaev,A., Bass,I., Nikiforov,V. and Goldfarb,A. (2003) Unified two-metal mechanism of RNA synthesis and degradation by RNA polymerase. EMBO J., 22, 2234-2244.