Enzymatic transition states and transition state analogues

Current Opinion in Structural Biology

Volumn 15, Issue 6, 2005, Pages 604-613

  Schramm, Vern L ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; ENZYME; OROTATE PHOSPHORIBOSYLTRANSFERASE; PROTEIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE; TRIOSEPHOSPHATE ISOMERASE;

BINDING AFFINITY; CATALYSIS; ENZYME ACTIVITY; ENZYME BINDING; ENZYME STRUCTURE; PHASE TRANSITION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; QUANTUM MECHANICS; REVIEW; THERMODYNAMICS; X RAY CRYSTALLOGRAPHY;

ANIMALS; CATALYSIS; CATALYTIC DOMAIN; ENZYMES; ESCHERICHIA COLI PROTEINS; HUMANS; MODELS, MOLECULAR; N-GLYCOSYL HYDROLASES; PROTEIN BINDING; PROTEIN CONFORMATION; PURINE-NUCLEOSIDE PHOSPHORYLASE; QUANTUM THEORY; THERMODYNAMICS;

EID: 27944458409     PISSN: 0959440X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.sbi.2005.10.017     Document Type: Review

References (49)

1. H. Eyring The activated complex in chemical reactions J Chem Phys 3 1935 107 115
2. L. Pauling Chemical achievement and hope for the future Am Sci 36 1948 50 58
3. H. Eyring, and F.H. Johnson The elastomeric rack in biology Proc Natl Acad Sci USA 68 1971 2341 2344
4. D.E. Koshland Jr. Correlation of structure and function in enzyme action Science 142 1963 1533 1541
5. R. Wolfenden Transition state analogues for enzyme catalysis Nature 223 1969 704 705
6. R. Wolfenden Transition state analog inhibitors and enzyme catalysis Annu Rev Biophys Bioeng 5 1976 271 306
7. E. Lolis, and G.A. Petsko Transition state analogues in protein crystallography: probes of the structural source of enzyme catalysis Annu Rev Biochem 59 1990 597 630
8. A. Fedorov, W. Shi, G. Kicska, E. Fedorov, P.C. Tyler, R.H. Furneaux, J.C. Hanson, G.J. Gainsford, J.Z. Larese, V.L. Schramm, and S.C. Almo Transition state structure of purine nucleoside phosphorylase and principles of atomic motion in enzymatic catalysis Biochemistry 40 2001 853 860
9. E. Pollak, and P. Talkner Reaction rate theory: where it was, where is it today, and where is it going? Chaos 15 2005 26116 A trip through the history of rate theory, including the proposals of Arrhenius (1889), Wigner (1932), Eyring (1935), Kramers (1940), Pechukas (1976), Chandler (1978) and Pollock (1986). Current problems are posed together with a summary of new directions for rate (transition state) theory.
10. M. Garcia-Viloca, J. Gao, M. Karplus, and D.G. Truhlar How enzymes work: analysis by modern rate theory and computer simulations Science 303 2004 186 195 Transition state theory, as applied by computer simulations, is explored in the context of enzymatic catalytic power. Using examples, it is proposed that all enzymatic rate enhancements can be explained by existing theory - lowering the free energy of activation and increasing the transmission coefficient. The 'quasi-thermodynamic free energy of activation' is used to indicate that equilibrium is not established at the transition state.
11. m ÷ rate for the uncatalyzed reaction in water. Of specific interest here is a thorough discussion of the remote binding interactions that contribute to catalysis and transition state stabilization. Classic examples of transition state structures are reviewed.
12. S.J. Benkovic, and S. Hammes-Schiffer A perspective on enzyme catalysis Science 301 2003 1196 1202 Dihydrofolate reductase is exemplified as an enzymatic scaffold for coupled dynamic networks of conserved residues that foster the formation of the transition state. Protein dynamic motion is shown to be central to catalysis, and the need for additional experimental and theoretical studies is emphasized.
13. K.F. Wong, T. Selzer, S.J. Benkovic, and S. Hammes-Schiffer Impact of distal mutations on the network of coupled motions correlated to hydride transfer in dihydrofolate reductase Proc Natl Acad Sci USA 102 2005 6807 6812
14. Z.X. Liang, and J.P. Klinman Structural bases of hydrogen tunneling in enzymes: progress and puzzles Curr Opin Struct Biol 14 2004 648 655 Hydrogen tunneling is highlighted by three enzyme systems, including soybean lipoxygenase-1, thermophilic alcohol dehydrogenase and dihydrofolate reductase. Particular attention has been devoted to the issues of whether protein dynamics modulate hydrogen tunneling probability and whether the tunneling process contributes to the catalytic power of enzymes.
15. X. Zhang, X. Zhang, and T.C. Bruice A definitive mechanism for chorismate mutase Biochemistry 44 2005 10443 10448 Computational chemistry is used to conclude that the formation of the NAC by the enzyme is the major contributor to catalysis. Computed transition state structures are similar in vacuum, in water or in the enzyme.
16. V.L. Schramm Enzymatic transition states: thermodynamics, dynamics and analogue design Arch Biochem Biophys 433 2005 13 26 The short lifetime of the transition state is emphasized to demonstrate that the dynamic nature of enzymatic transition states cannot be adequately described in thermodynamic terms, including transition state binding energy. It is proposed that transition states are reached by stochastic dynamic excursions of protein groups that participate in transition state formation. Transition state analogues capture dynamic energy and convert it into thermodynamic energy.
17. S. McClendon, N. Zhadin, and R. Callender The approach to the Michaelis complex in lactate dehydrogenase: the substrate binding pathway Biophys J 89 2005 2024 2032 Binding of NADH to lactate dehydrogenase occurs via an encounter complex followed by two unimolecular conformational adjustments on the microsecond to millisecond timescale, including the closure of the catalytic site loop. Thermodynamic analysis suggests that transient melting of 10-15% of the protein is involved in this structural alteration to align NADH in the catalytic site.
18. G.P. Wang, S.M. Cahill, X. Liu, M.E. Girvin, and C. Grubmeyer Motional dynamics of the catalytic loop in OMP synthase Biochemistry 38 1999 284 295
19. cat. This work confirms earlier NMR work by the McDermott group.
20. M. Karplus, and J. McCammon Dynamics of proteins: elements and functions Annu Rev Biochem 52 1983 263 300
21. L.W. Yang, and I. Bahar Coupling between catalytic site and collective dynamics: a requirement for mechanochemical activity of enzymes Structure 13 2005 893 904
22. M. Wolf-Watz, V. Thai, K. Henzler-Wildman, G. Hadjipavlou, E.Z. Eisenmesser, and D. Kern Linkage between dynamics and catalysis in a thermophilic-mesophpilic enzyme pair Nat Struct Mol Biol 11 2004 945 949
23. D. Antoniou, M.R. Abolfath, and S.D. Schwartz Transition path sampling of classical rate-promoting vibrations J Chem Phys 121 2004 6442 6447 Attempts were made to explain enzymatic proton transfer reactions that include quantum tunneling. An equivalent classical chemical problem was evaluated, and dynamic atomic motion was found to contain slow and fast oscillations optimal for catalysis but outside current concepts of transition state theory.
24. T.C. Bruice A view at the millennium: the efficiency of enzymatic catalysis Acc Chem Res 35 2002 139 148
25. J. Luo, and T.C. Bruice Anticorrelated motions as a driving force in enzyme catalysis: the dehydrogenase reaction Proc Natl Acad Sci USA 101 2004 13152 13156
26. J.A. Gerlt, M.M. Kreevoy, W. Cleland, and P.A. Frey Understanding enzymic catalysis: the importance of short, strong hydrogen bonds Chem Biol 4 1997 259 267
27. D. Neidhart, Y. Wei, C. Cassidy, J. Lin, W.W. Cleland, and P.A. Frey Correlation of low- barrier hydrogen bonding and oxyanion binding in transition state analogue complexes of chymotrypsin Biochemistry 40 2001 2439 2447
28. S. Núñez, D. Antoniou, V.L. Schramm, and S.D. Schwartz Promoting vibrations in human purine nucleoside phosphorylase. A molecular dynamics and hybrid quantum mechanical/molecular mechanical study J Am Chem Soc 126 2004 15720 15729 Classical and mixed quantum/classical MD simulations were performed to assess the existence of protein-facilitated promoting vibrations. The hybrid QM/MM methods were used to consider whether an enzymatic vibration that pushes oxygens of PNP together is coupled to the reaction coordinate. The calculations revealed the existence of promoting vibrations coupled to the reaction coordinate.
29. A. Soudackov, E. Hatcher, and S. Hammes-Schiffer Quantum and dynamical effects of proton donor-acceptor vibrational motion in nonadiabatic proton-coupled electron transfer reactions J Chem Phys 122 2005 14505
30. S. Hammes-Schiffer Quantum-classical simulation methods for hydrogen transfer in enzymes: a case study of dihydrofolate reductase Curr Opin Struct Biol 14 2004 192 201
31. H.O. Pritchard Recrossings and transition-state theory J Phys Chem 109 2005 1400 1404 Computational chemistry using simple chemical isomerization demonstrates transition state recrossings. Some reacting molecules cross the transition state 'balance point' but return to reactant before going to product, making the transmission coefficient near 0.5.
32. Z.X. Liang, I. Tsigos, T. Lee, V. Bouriotis, K.A. Resing, N.G. Ahn, and J.P. Klinman Evidence for increased local flexibility in psychrophilic alcohol dehydrogenase relative to its thermophilic homologue Biochemistry 43 2004 14676 14683
33. Z.X. Liang, T. Lee, K.A. Resing, N.G. Ahn, and J.P. Klinman Thermal-activated protein mobility and its correlation with catalysis in thermophilic alcohol dehydrogenase Proc Natl Acad Sci USA 101 2004 9556 9561
34. R.P. Venkitakrishnan, E. Zaborowski, D. McElheny, S.J. Benkovic, H.J. Dyson, and P.E. Wright Conformational changes in the active site loops of dihydrofolate reductase during the catalytic cycle Biochemistry 43 2004 16046 16055
35. R.S. Sikorski, L. Wang, K.A. Markham, P.T. Rajagopalan, S.J. Benkovic, and A. Kohen Tunneling and coupled motion in the Escherichia coli dihydrofolate reductase catalysis J Am Chem Soc 126 2004 4778 4779
36. C. Mao, W.J. Cook, M. Zhou, A.A. Federov, S.C. Almo, and S.E. Ealick Calf spleen purine nucleoside phosphorylase complexed with substrates and substrate analogues Biochemistry 37 1998 7135 7146
37. G.A. Kicska, P.C. Tyler, G.B. Evans, R.H. Furneaux, W. Shi, and A. Fedorov Atomic dissection of the hydrogen bond network for transition-state analogue binding to purine nucleoside phosphorylase Biochemistry 41 2002 14489 14498
38. A. Lewandowicz, E.A. Taylor Ringia, L.M. Ting, K. Kim, P.C. Tyler, G.B. Evans, O.V. Zubkova, S. Mee, G.F. Painter, and D.H. Lenz Energetic mapping of transition state analogue interactions with human and Plasmodium falciparum purine nucleoside phosphorylases J Biol Chem 280 2005 30320 30328 The binding of different transition state analogues (derived from specific atomic alterations of immucillin-H) was measured at the catalytic sites of human and malarial PNP. This study demonstrates remarkable differences in the binding of transition state analogues among PNP isozymes. Energetic mapping of PNP-immucillin-H binding energy gives ∼30 kcal/mol, whereas the catalytic rate enhancement of PNP is ∼18 kcal/mol. Binding interactions are strongly cooperative.
39. V. Singh, W. Shi, G.B. Evans, P.C. Tyler, R.H. Furneaux, S.C. Almo, and V.L. Schramm Picomolar transition state analogue inhibitors of human 5′-methylthioadenosine phosphorylase and X-ray structure with MT-immucillin-A Biochemistry 43 2004 9 18 Based on the ribooxacarbenium ion character of N-ribosyltransferase transition states, transition state analogues were designed, synthesized as described in [40] and co-crystallized with human MTAP. Differences in catalytic site contacts between substrate-bound and transition state complexes are modest.
40. G.B. Evans, R.H. Furneaux, D.H. Lenz, G.F. Painter, V.L. Schramm, V. Singh, and P.C. Tyler Second generation transition state analogue inhibitors of human 5′- methylthioadenosine phosphorylase J Med Chem 48 2005 4679 4689
41. -15 M).
42. J.E. Lee, V. Singh, G.B. Evans, P.C. Tyler, R.H. Furneaux, K.A. Cornell, M.K. Riscoe, V.L. Schramm, and P.L. Howell Structural rationale for the affinity of pico- and femtomolar transition state analogues of Escherichia coli 5′- methylthioadenosine/S-adenosylhomocysteine nucleosidase J Biol Chem 280 2005 18274 18282 Crystal structures of MTAN complexed with transition state analogues were determined to 2.2 Å resolution, and compared with other MTAN-inhibitor complexes. These are among the tightest binding enzyme-ligand complexes ever described; analysis of their mode of binding provides extraordinary insight into the structural basis of their affinity. The MTAN-inhibitor complex reveals the presence of a new ion pair, between the 4′-iminoribitol atom and the nucleophilic water (WAT3), that captures key features of the transition state.
43. V.L. Schramm Enzymatic transition states and transition state analog design Annu Rev Biochem 67 1998 693 720
44. F. Wang, W. Shi, E. Nieves, R.H. Angeletti, V.L. Schramm, and C. Grubmeyer A transition-state analogue reduces protein dynamics in hypoxanthine-guanine phosphoribosyltransferase Biochemistry 40 2001 8043 8054
45. I.D. Kuntz, K. Chen, K.A. Sharp, and P.A. Kollman The maximal affinity of ligands Proc Natl Acad Sci USA 96 1999 9997 10002
46. ••] to design transition state analogues.
47. A. Krasiński, Z. Radić, R. Manetsch, J. Raushel, P. Taylor, K.B. Sharpless, and H.C. Kolb In situ selection of lead compounds by click chemistry: target-guided optimization of acetylcholinesterase inhibitors J Am Chem Soc 127 2005 6686 6687 Using tacrine and phenylphenanthridinium reagent libraries, reactions occur preferentially within the catalytic site of acetylcholinesterase to tailor-fit two halves of extended hydrophobic cations into the catalytic site. Dissociation constants as low as 33 fM are obtained.
48. K.N. Houk, A.G. Leach, S.P. Kim, and X. Zhang Binding affinities of host-guest, protein-ligand and protein-transition-state complexes Angew Chem Int Ed Engl 42 2003 4872 4897 The binding affinity of complexes, including Michaelis complexes, is roughly equivalent to the surface area buried upon complex formation. Enzyme-transition state analogue complexes bind more tightly than predicted from the area because of close contacts within the complex, but explaining the transition state analogue binding energy "remains a significant challenge".
49. X. Zhang, and K.N. Houk Why enzymes are proficient catalysts: beyond the Pauling paradigm Acc Chem Res 38 2005 379 385 Catalytic proficiency is explained by the 'covalent hypothesis', which proposes that all proficient enzymes have covalent interactions between enzyme and the transition state. Only modestly proficient enzymes are proposed to operate by non-covalent transition state binding mechanisms. This surprising proposal requires a new definition of covalent bonds before it becomes useful for enzymology.