Binding isotope effects: boon and bane

Current Opinion in Chemical Biology

Volumn 11, Issue 5, 2007, Pages 529-536

  Schramm, Vern L ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOSE; HEXOKINASE; HYDRIDE ION; ISOTOPE; LACTATE DEHYDROGENASE; LIGAND; PROTON; PURINE NUCLEOSIDE PHOSPHORYLASE; THYMIDINE PHOSPHORYLASE; TRITIUM; UNCLASSIFIED DRUG;

CHEMICAL BINDING; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; ENZYME CONFORMATION; ENZYME MECHANISM; GEOMETRY; HUMAN; IMMOBILIZATION; ISOTOPE ANALYSIS; KINETIC ISOTOPE EFFECT; MACROMOLECULE; MEASUREMENT; MOLECULAR INTERACTION; NONHUMAN; QUANTUM MECHANICS; REACTION ANALYSIS; REVIEW; STRUCTURE ANALYSIS;

DRUG EVALUATION, PRECLINICAL; ENZYMES; ISOTOPES; KINETICS; LIGANDS; PROTEIN BINDING;

EID: 35348833510     PISSN: 13675931     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cbpa.2007.07.013     Document Type: Review

References (43)

1. In: Melander L. (Ed). Isotope Effects on Reaction Rates (1960), Ronald Press, NY
2. Bender M.L., and Hamilton G.A. Kinetic isotope effects of deuterium oxide on several a-chymotrypsin-catalyzed reactions. J Am Chem Soc 84 (1962) 2570-2577
3. Thomson J.F. Fumarase activity in D2O. Arch Biochem Biophys 90 (1962) 1-6
4. Westheimer F.H. The magnitude of the primary kinetic isotope effect for compounds of hydrogen and deuterium. Chem Rev 61 (1961) 265-273
5. In: Cleland W.W., O'Leary M.H., and Northrop D.B. (Eds). Isotope Effects on Enzyme-Catalyzed Reactions (1977), University Park Press, Baltimore, MD
6. Buddenbaum W.E., and Shiner Jr. V.J. Isotope Effects on Enzyme-Catalyzed Reactions (1977), University Park Press, Baltimore, MD pp. 1-36
7. Berti P.J. Determining transition states from kinetic isotope effects. Methods Enzymol 308 (1999) 355-397
8. Northrop D.B. The expression of isotope effects on enzyme-catalyzed reactions. Annu Rev Biochem 50 (1981) 103-131
9. Cleland W.W. Isotope effects: determination of enzyme transition state structure. Methods Enzymol 249 (1995) 341-373
10. Schramm V.L. Enzymatic transition-state analysis and transition-state analogs. Methods Enzymol 308 (1999) 301-355
11. Ruszczycky M.W., and Anderson V.E. Interpretation of V/K isotope effects for enzymatic reactions exhibiting multiple isotopically sensitive steps. J Theor Biol 243 (2006) 328-342. Realistic enzymatic complexity is examined for the contribution of individual steps in the reaction to the experimentally measured V/K isotope effects. An essential primer for scientists in this field.
12. Lewis B.E., and Schramm V.L. Enzymatic binding isotope effects and the interaction of glucose with hexokinase. In: Kohen A., and Limbach H.-H. (Eds). Isotope Effects in Chemistry and Biology (2006), CRC Taylor & Francis, Boca Raton 1019-1053. This study examines atomic contributions to binding isotope effects using a combination of experimental and computational examples with the human brain hexokinase and its binding of specifically labeled glucoses. Effect of equilibrating substrate (α-anomers and β-anomers for glucose) is considered as a general case.
13. Anderson V.E. Quantifying energetic contributions to ground state destabilization. Arch Biochem Biophys 433 (2005) 27-33. Substrate binding to enzymes invariably causes conformational changes in both the protein and the reactant. The energetic changes can be estimated by a combination of spectroscopic and computational methods and pertinent examples are given.
14. + to lactate dehydrogenase. Biochemistry 28 (1989) 3619-3624
15. 18O]oxamate with NADH and lactate dehydrogenase. Biochemistry 34 (1995) 6050-6058
16. Pineda T., Callender R., and Schwartz S.D. Ligand binding and protein dynamics in lactate dehydrogenase. Biophys J 93 (2007) 1474-1483. Molecular dynamics calculations are used to explore the motions lactate dehydrogenase undergoes to permit substrate entry into the relatively closed catalytic site. Subtle protein and solvent reorganization permits binding. The structures shown in Figure 2 are taken from this paper.
17. Horenstein B.A., and Schramm V.L. Correlation of the molecular electrostatic potential surface of an enzymatic transition state with novel transition-state inhibitors. Biochemistry 32 (1993) 9917-9925
18. Degano M., Almo S.C., Sacchettini J.C., and Schramm V.L. Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor. Biochemistry 37 (1998) 6277-6285
19. Gawlita E., Lantz M., Paneth P., Bell A.F., Tonge P.J., and Anderson V.E. H-bonding in alcohols is reflected in the C-H bond strength: variation of C-D vibrational frequency and fractionation factor. J Am Chem Soc 122 (2000) 11660-11669
20. Lewis B.E., and Schramm V.L. Binding equilibrium isotope effects for glucose at the catalytic domain of human brain hexokinase. J Am Chem Soc 125 (2003) 4785-4798
21. Lewis B.E., and Schramm V.L. Glucose binding isotope effects in the ternary complex of brain hexokinase demonstrate partial relief of ground-state destabilization. J Am Chem Soc 125 (2003) 4672-4673
22. Lewis B.E., Choytun N., Schramm V.L., and Bennet A.J. Transition states for glucopyranose interconversion. J Am Chem Soc 128 (2006) 5049-5058. One of the oldest questions in carbohydrate chemistry is solved by the application of equilibrium and kinetic isotope effects. Transition states are formed with multiple water molecules and a single water molecule spanning the hydroxyl groups on C1 and C5 cannot explain the results.
23. Temmink O.H., de Bruin M., Turksma A.W., Cricca S., Laan A.C., and Peters G.J. Activity and substrate specificity of pyrimidine phosphorylases and their role in fluoropyrimidine sensitivity in colon cancer cell lines. Int J Biochem Cell Biol 39 (2007) 565-575
24. Birck M.R., and Schramm V.L. Nucleophilic participation in the transition state for human thymidine phosphorylase. J Am Chem Soc 126 (2004) 2447-2453
25. Edwards P.N. A kinetic, modeling and mechanistic re-analysis of thymidine phosphorylase and some related enzymes. J Enzyme Inhib Med Chem 21 (2006) 483-499
26. McNally V.A., Gbaj A., Douglas K.T., Stratford I.J., Jaffar M., Freeman S., and Bryce R.A. Identification of a novel class of inhibitor of human and Escherichia coli thymidine phosphorylase by in silico screening. Bioorg Med Chem Lett 13 (2003) 3705-3709
27. Priego E.M., Mendieta J., Gago F., Balzarini J., De Clercq E., Camarasa M.J., and Perez-Perez M.J. Towards new thymidine phosphorylase/PD-ECGF inhibitors based on the transition state of the enzyme reaction. Nucleosides Nucleotides Nucleic Acids 22 (2003) 951-953
28. 3H]thymidine kinetic isotope effect in human thymidine phosphorylase. J Am Chem Soc 126 (2004) 6882-6883
29. El Omari K., Bronckaers A., Liekens S., Perez-Perez M.J., Balzarini J., and Stammers D.K. Structural basis for non-competitive product inhibition in human thymidine phosphorylase: implications for drug design. Biochem J 399 (2006) 199-204
30. Norman R.A., Barry S.T., Bate M., Breed J., Colls J.G., Ernill R.J., Luke R.W., Minshull C.A., McAlister M.S., McCall E.J., et al. Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor. Structure 12 (2004) 75-84
31. CH Correlates with alcohol hydrogen bond strength. J Org Chem 71 (2006) 2878-2880
32. Ravandi F., and Gandhi V. Novel purine nucleoside analogues for T-cell-lineage acute lymphoblastic leukaemia and lymphoma. Expert Opin Investig Drugs 15 (2006) 1601-1613
33. Galmarini C.M. Drug evaluation: forodesine-PNP inhibitor for the treatment of leukemia, lymphoma and solid tumor. IDrugs 9 (2006) 712-722
34. Miles R.W., Tyler P.C., Furneaux R.H., Bagdassarian C.K., and Schramm V.L. Purine nucleoside phosphorylase. Transition state structure, transition state inhibitors and one-third-the-sites reactivity. In: Frey P.A., and Northrop D.B. (Eds). Enzymatic Mechanisms (1999), IOS Press, Washington DC 32-47
35. Lewandowicz A., Taylor Ringia E.A., Ting L.M., Kim K., Tyler P.C., Evans G.B., Zubkova O.V., Mee S., Painter G.F., Lenz D.H., et al. Energetic mapping of transition state analogue interactions with human and Plasmodium falciparum purine nucleoside phosphorylases. J Biol Chem 280 (2005) 30320-30328. Binding interactions of individual atomic sites on transition state analogues cause cooperative binding to their target enzymes. The sum of ΔΔG values for individual atomic substitutions is greater than for the intact inhibitor. These support remote BIE interactions from energetic interactions far from the site of chemistry.
36. Balakrishnan K., Nimmanapalli R., Ravandi F., Keating M.J., and Gandhi V. Forodesine, an inhibitor of purine nucleoside phosphorylase, induces apoptosis in chronic lymphocytic leukemia cells. Blood 108 (2006) 2392-2398
37. Lewandowicz A., and Schramm V.L. Transition state analysis for human and Plasmodium falciparum purine nucleoside phosphorylases. Biochemistry 43 (2004) 1458-1468
38. Fedorov A., Shi W., Kicska G., Fedorov E., Tyler P.C., Furneaux R.H., Hanson J.C., Gainsford G.J., Larese J.Z., Schramm V.L., and Almo S.C. Transition state structure of purine nucleoside phosphorylase and principles of atomic motion in enzymatic catalysis. Biochemistry 40 (2001) 853-860
39. 3H remote position of PNP are measured and compared with intrinsic V/K KIE to fully resolve binding and chemical-step isotope effects. Mutation of His257 (in H-bond contact with the 5′-hydroxyl group) causes changes in both BIE and KIE to demonstrate the broad range of normal and inverse BIE coupled to remote regions of the catalytic site.
40. 3H1 (anomeric carbon) bond of adenosine in V/K isotope effect measurements. At five bonds remote from the site of chemistry, and differing for the three enzymes reported here, this remote effect has the hallmarks of a BIE. Not previously appreciated, this effect may have its origin in the glycosyl torsion angle between the purine and the ribosyl group, making it of potential use in reactions involving nucleic acids.
41. Aleshin A.E., Zeng C., Bourenkov G.P., Bartunik H.D., Fromm H.J., and Honzatko R.B. The mechanism of regulation of hexokinase: new insights from the crystal structure of recombinant human brain hexokinase complexed with glucose and glucose-6-phosphate. Structure 6 (1998) 39-50
42. 2 V/K kinetic isotope effects seen in enzymes are a result of binding distortions combined with transition state interactions.
43. Nunez S., Wing C., Antoniou D., Schramm V.L., and Schwartz S.D. Insight into catalytically relevant correlated motions in human purine nucleoside phosphorylase. J Phys Chem A 110 (2006) 463-472. Computational analysis of the dynamic vibrational patterns of human PNP involves coupling the protein motions to His257, which, in turn, causes a compression dynamic mode between the 4′-ring oxygen and the 5′-hydroxyl oxygen of inosine at the catalytic site.