Challenging a paradigm: Theoretical calculations of the protonation state of the Cys25-His159 catalytic diad in free papain

Proteins: Structure, Function and Bioinformatics

Volumn 77, Issue 4, 2009, Pages 916-926

  Shokhen, Michael ^a   Khazanov, Netaly ^a   Albeck, Amnon ^a  

^a BAR ILAN UNIVERSITY   (Israel)

Author keywords

Cysteine proteases; Enzyme mechanism; Molecular modeling; pK a in proteins; Quantum mechanics; Solvation

Indexed keywords

CYSTEINE PROTEINASE; PAPAIN;

ARTICLE; CALCULATION; CATALYSIS; KINETICS; MOLECULAR DYNAMICS; MOLECULAR MODEL; NUCLEAR MAGNETIC RESONANCE; PKA; PRIORITY JOURNAL; PROTEIN STRUCTURE; PROTON TRANSPORT; THEORETICAL STUDY; X RAY CRYSTALLOGRAPHY;

CATALYTIC DOMAIN; CYSTEINE; HISTIDINE; HYDROGEN BONDING; KINETICS; MODELS, MOLECULAR; NUCLEAR MAGNETIC RESONANCE, BIOMOLECULAR; PAPAIN; PROTEIN CONFORMATION; PROTONS; STATIC ELECTRICITY; THERMODYNAMICS; WATER;

BACTERIA (MICROORGANISMS);

EID: 70450211370     PISSN: 08873585     EISSN: 10970134     Source Type: Journal    
DOI: 10.1002/prot.22516     Document Type: Article

References (69)

1. Storer AC, Menard R. Catalytic mechanism in papain family of cysteine peptidases. Methods Enzymol 1994;244:486-500.
2. Otto H-H, Schirmeister T. Cysteine proteases and their inhibitors. Chem Rev 1997;97:133-171.
3. Polgar L. Catalytic mechanisms of cysteine peptidases. In: Barrett AJ, Rawlings ND, Woessner JF, editors. Handbook of proteolytic enzymes, 2nd ed. London: Elsevier; 2004. pp 1072-1079.
4. Polgar L. On the mode of activation of the catalytically essential sulfhydryl group of papain. Eur J Biochem 1973;33:104-109.
5. Polgar L. Spectrophotometric determination of mercaptide ion, an activated form of SH-group in thiol enzymes. FEBS Lett 1974;38:187-190.
6. Polgar L. Mercaptide-imidazolium ion-pair: the reactive nucleophile in papain catalysis. FEBS Lett 1974;47:15-18.
7. Dawson RMC, Elliott DC, Elliott WH, Jones KM. Data for biochemical research, 3rd ed. Oxford: Oxford Science Publications; 1986. pp 1-31.
8. Johnson FA, Lewis SD, Shafer JA. Perturbations in the free energy and enthalpy of ionization of histidine-159 at the active site of papain as determined by fluorescence spectroscopy. Biochemistry 1981;20:44-48.
9. Johnson FA, Lewis SD, Shafer JA. Determination of low pK for histidine-159 in the S-methylthio derivative of papain by proton nuclear magnetic resonance spectroscopy. Biochemistry 1981;20:44-48.
10. Lewis SD, Johnson FA, Shafer JA. Effect of cysteine-25 on the ionization of histidine-159 in papain as determined by proton nuclear magnetic resonance spectroscopy. Evidence for His-159-Cys-25 ion pair and its possible role in catalysis. Biochemistry 1981;20:48-51.
11. Willenbrock F, Brocklehurst K. Natural structural variation in enzymes as a tool in the study of mechanism exemplified by a comparison of the catalytic-site structure and characteristics of cathepsin B and papain. pH-dependent kinetics of the reactions of cathepsin B from bovine spleen and from rat liver with a thiol-specific two-protonic-state probe (2,2′-dipyridyl disulphide) and with a specific synthetic substrate (N-alpha-benzyloxycarbonyl-L-arginyl-L-arginine 2-naphthylamide). Biochem J 1984;222:805-814.
12. Mellor GW, Patel M, Thomas EW, Brocklehurst K. Clarification of the pH-dependent kinetic behaviour of papain by using reactivity probes and analysis of alkylation and catalysed acylation reactions in terms of multihydronic state models: implications for electrostatics calculations and interpretation of the consequences of site-specific mutations such as Asp-158-Asn and Asp-158-Glu. Biochem J 1993;294:201-210. (Pubitemid 23251931)
13. Thomas MP, Topham CM, Kowlessur D, Mellor GW, Thomas EW, Whitford D, Brocklehurst K. Structure of chymopapain M the late-eluted chymopapain deduced by comparative modelling techniques and active-centre characteristics determined by pH-dependent kinetics of catalysis and reactions with time-dependent inhibitors: the Cys-25/His-159 ion-pair is insufficient for catalytic competence in both chymopapain M and papain. Biochem J 1994;300:805-820. (Pubitemid 24180598)
14. Pinitglang S, Watts AB, Patel M, Reid JD, Noble MA, Gul S, Bokth A, Naeem A, Patel H, Thomas EW, Sreedharan SK, Verma C, Brocklehurst K. A classical enzyme active center motif lacks catalytic competence until modulated electrostatically. Biochemistry 1997;36:9968-9982. (Pubitemid 27357705)
15. Noble MA, Gul S, Verma CS, Brocklehurst K. Ionization characteristics and chemical influences of aspartic acid residue 158 of papain and caricain determined by structure-related kinetic and computational techniques: multiple electrostatic modulators of active-centre chemistry. Biochem J 2000;351:723-733. (Pubitemid 30835753)
16. Hussain S, Pinitglang S, Bailey TS, Reid JD, Noble MA, Resmini M, Thomas EW, Greaves RB, Verma CS, Brocklehurst K. Variation in the pH-dependent pre-steady-state and steady-state kinetic characteristics of cysteine-proteinase mechanism: evidence for electrostatic modulation of catalytic-site function by the neighbouring carboxylate anion. Biochem J 2003;372:735-746. (Pubitemid 36760387)
17. Menard R, Khouri HE, Plouffe C, Dupras R, Rippol D, Vernet T, Tessier DC, Lalberte F, Thomas DY, Storer AC. A protein engineering study of the role of aspartate 158 in the catalytic mechanism of papain. Biochemistry 1990;29:6706-6713. (Pubitemid 20223567)
18. Menard R, Khouri HE, Plouffe C, Laflamme P, Dupras R, Vernet T, Tessier DC, Thomas DY, Storer AC. Importance of hydrogen-bonding interactions involving the side chain of Asp158 in the catalytic mechanism of papain. Biochemistry 1991;30:5531-5538.
19. Gul S, Hussain S, Thomas MP, Resmini M, Verma CS, Thomas EW, Brocklehurst K. Generation of nucleophilic character in the Cys25/His159 ion-pair of papain involves Trp177 but not Asp 158. Biochemistry 2008;47:2025-2035. (Pubitemid 351287128)
20. Sarkany Z, Szeltner Z, Polgar L. Thiolate-imidazolium ion pair id not obligatory catalytic entity of cysteine peptidases: the active site of picornain 3C. Biochemistry 2001;40:10601-10606. (Pubitemid 32816671)
21. Huang C, Wei P, Fan K, Liu Y, Lai L. 3C-like proteinase from SARS coronavirus catalyzes substrate hydrolysis by a general base mechanism. Biochemistry 2004;43:4568-4574. (Pubitemid 38500585)
22. Eichinger A, Beisel HG, Jacob U, Huber R, Medrano FJ, Banbula A, Potempa J, Travis J, Bode W. Inhibition of trypsin-like cysteine proteinases (Gingipains) from Porphyromonas gingivalis by tetracycline and its analogues. EMBO J 1999;18:5453-5462.
23. Warshel A. Energetics of enzyme catalysis. Proc Natl Acad Sci USA 1978;11:5250-5254.
24. Hwang J-K, Warshel A. Why ion pair reversal by protein engineering is unlikely to succeed. Nature 1988;334:270-272.
25. Warshel A. Calculations of enzymatic reactions: calculations of pKa, proton transfer reactions, and general acid catalysis reactions in enzymes. Biochemistry 1981;20:3167-3177.
26. Warshel A, Russel S. Theoretical correlation of structure and energetics in the catalytic reaction of trypsin. J Am Chem Soc 1986;108:6569-6579.
27. Cutler RL, Davies AM, Creighton S, Warshel A, Moore JR, Smith M, Mauk AG. Role of arginine-38 in regulation of the cytochrome c oxidation-reduction equilibrium. Biochemistry 1989;28:3188-3197. (Pubitemid 19121911)
28. Schutz CN, Warshel A. The low barrier hydrogen bond (LBHB) proposal revisited: the case of the Asp. . . His pair in serine proteases. Proteins 2004;55:711-723.
29. Warshel A. Computer modeling of chemical reactions in enzymes and solutions. New York: John Wiley & Sons; 1991. pp 140-146.
30. Lee FS, Chu ZT, Warshel A. Microscopic and semimicroscopic calculations of electrostatic energies in proteins by POLARIS and ENZYMIX programs. J Comput Chem 1993;14:161-185.
31. Harrison MJ, Burton NA, Hillier IH. Catalytic mechanism of the enzyme papain: predictions with a hybrid quantum mechanical/molecular mechanical potential. J Am Chem Soc 1997;119:12285-12291.
32. Ma S, Devi-Kesavan LS, Gao J. Molecular dynamics simulations of the catalytic pathway of a cysteine protease: a combined QM/MM study of human cathepsin K. J Am Chem Soc 2007;129:13633-13645. (Pubitemid 350071792)
33. Mladenovic M, Schirmeister T, Thiel S, Thiel W, Engels B. The importance of the active site histidine for the activity of epoxide- or aziridine-based inhibitors of cysteine proteases. ChemMedChem 2007;2:120-128.
34. Mladenovic M, Fink RF, Thiel W, Schirmeister T, Engels B. On the origin of stabilization of the zwitterionic resting state of cysteine proteases: a theoretical study. J Am Chem Soc 2008;130:8696-8705. (Pubitemid 351962503)
35. Shokhen M, Khazanov N, Albeck A. Screening of the active site from water by the incoming ligand triggers catalysis and inhibition in serine proteases. Proteins 2008;70:1578-1587. (Pubitemid 351304114)
36. Shokhen M, Albeck A. Is there a weak H-bond → LBHB transition upon tetrahedral complex formation in serine proteases? Proteins 2004;54:468-477.
37. Shokhen M, Albeck A. Identification of protons position in acid-base enzyme catalyzed reactions: the hepatitis C viral NS3 protease. Proteins 2004;55:245-250. (Pubitemid 38437484)
38. Ozeri R, Khazanov N, Perlman N, Shokhen M, Albeck A. Enzyme Isoselective inhibitors: a novel tool for binding trend analysis. ChemMedChem 2006;1:631-638. (Pubitemid 44105789)
39. Shokhen M, Khazanov N, Albeck A. Enzyme isoselective inhibitors: application to drug design. ChemMedChem 2006;1:639-643. (Pubitemid 44105790)
40. Shokhen M, Khazanov N, Albeck A. The cooperative effect between active site ionized groups and water desolvation controls the alteration of acid/base catalysis in serine proteases. ChemBioChem 2007;8:1416-1421. (Pubitemid 47300335)
41. Liang TC, Abeles RH. Complex of g-chymotrypsin and N-acetyl-L-leucyl-L- phenylalanyl trifluoromethyl ketone: structural studies with NMR spectroscopy. Biochemistry 1987;26:7603-7608.
42. Cassidy CS, Lin J, Frey PA. A new concept for the mechanism of action of chymotrypsin: the role of the low-barrier hydrogen bond. Biochemistry 1997;36:4576-4584. (Pubitemid 27180306)
43. Kamphuis IG, Kalk KH, Swarte MB, Drenth J. Structure of papain refined at 1.65 A resolution. J Mol Biol 1984;179:233-256.
44. Maestro 5. Portland, OR: Schrödinger, Inc; 1991-2004.
45. Kaminski GA, Friesner RA, Tirad-Rives J, Jorgensen WL. Evaluation of reparametrization of the OPLS AA force field for proteins via comparison with accurate quantum chemical calculations on peptides. J Phys Chem B 2001;105:6474-6487.
46. Macromodel 7. Portland, OR: Schrödinger, Inc; 1991-2004.
47. Chang G, Guida WC, Still WC. An internal-coordinate Monte Carlo method for searching conformational space. J Am Chem Soc 1989;11:4379-4386.
48. Saunders M, Houk KN, Wu YD, Still WC, Lipton M, Chang G, Guida WC. Conformations of cycloheptadecane. A comparison of methods for conformational searching. J Am Chem Soc 1990;112:1419-1427.
49. JAGUAR 5.1. Portland, OR: Schrödinger, Inc; 1991-2004.
50. Tannor DJ, Marten B, Murphy R, Friesner RA, Sitcoff D, Nicholls A, Honig B, Ringnalda M, Goddard III WA. Accurate first principles calculation of molecular charge distributions and solvation energies from ab initio quantum mechanics and continuum dielectric theory. J Am Chem Soc 1994;116:11875-11882.
51. Marten B, Kim K, Cortis C, Friesner RA, Murphy RB, Ringnalda MN, Sitcoff D, Honig B. A new model for calculation of solvation free energies: correction of self-consistent reaction field continuum dielectric theory for short range hydrogen-bonding effects. J Phys Chem 1996;100:11775-11788. (Pubitemid 126788600)
52. Friezner RA, Murphy RB, Beachy MD, Ringnalda MN, Pollard WT, Dunietz BD, Cao Y. Correlated ab initio electronic structure calculations for large molecules. J Phys Chem A 1999;103:1913-1928.
53. Murphy RB, Cao Y, Beachy MD, Ringalda MN, Friesner RA. Efficient pseudospectral methods for density functional calculations. J Chem Phys 2000;112:10131-10141. (Pubitemid 30876823)
54. Hunter EPL, Lias SG. Evaluated gas phase basicities and proton affinities of molecules: an update. J Phys Chem Ref Data 1998;27:413-656. (Pubitemid 128094168)
55. Taft RW, Bordwell FG. Structural and solvent effects evaluated from acidities measured in dimethyl sulfoxide and in the gas phase. Acc Chem Res 1988;21:463-469.
56. a prediction module. Schrödinger, Inc. Available at: http://yfaat.ch.huji.ac.il/jaguar-help/ mank.html.
57. Lide DR. CRC handbook of chemistry and physics, 88th ed. New York: CRC Press; 2007-2008.
58. Danehly JP, Noel CJ. The relative nucleophilic character of several mercaptans toward ethylene oxide. J Am Chem Soc 1960;82:2511-2515.
59. Kreevoy MM, Harper ET, Duvall RE, Wilgus HS, Ditsch LT. Inductive effects on the acid dissociation constant of mercaptans. J Am Chem Soc 1960;82:4899-4902.
60. Topol IA, Tawa GJ, Burt SK, Rashin AA. Calculation of absolute and relative acidities of substituted imidazoles in aqueous solvent. J Phys Chem A 1997;101:10075-10081.
61. Levin IN, Physical chemistry, 3rd ed. Chapter 22. New York: McGraw-Hill; 1988.
62. Wang J, Cieplak P, Kollman PA. How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? J Comput Chem 2000;21:1049-1074.
63. Essman U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG. A smooth particle mesh Ewald method. J Chem Phys 1995;103:8577-8593.
64. a prediction by Ewald summation. J Mol Graph Model 2006;25:481-486.
65. Yasara Dynamics. Available at: www.yasara.org.
66. Cao Y, Beachy MD, Braden DA, Morril LA, Ringalda MN, Friezner RA. Nuclear-magnetic-resonance shielding constants calculated by pseudospectral methods. J Chem Phys 2005;122:224116.
67. Lee KK, Fitch CA, Garcia-Moreno EB. Distance dependence and salt sensitivity of pairwise, coulombic interactions in a protein. Prot Sci 2002;11:1004-1101.
68. Kuhn P, Knapp M, Soltis SM, Ganshaw G, Thoene M, Bott R. The 0.78 Å Structure of a serine protease: Bacillus lentus subtilisin. Biochemistry 1998;37:13446-13452.
69. Katona G, Wilmouth RC, Wright PA, Berglund GI, Hajdu J, Neutze R, Schofield CJ. X-ray structure of a serine protease acyl-enzyme complex at 0.95-Å resolution. J Biol Chem 2002;277:21962-21970. (Pubitemid 34952351)