The GAP arginine finger movement into the catalytic site of Ras increases the activation entropy

Proceedings of the National Academy of Sciences of the United States of America

Volumn 105, Issue 17, 2008, Pages 6260-6265

  Kötting, Carsten ^a   Kallenbach, Angela ^a   Suveyzdis, Yan ^a   Wittinghofer, Alfred ^b   Gerwert, Klaus ^a  

^a RUHR UNIVERSITY BOCHUM   (Germany)

^b MAX PLANCK INSTITUTE OF MOLECULAR PHYSIOLOGY   (Germany)

Author keywords

Enzyme catalysis; FTIR spectroscopy; GTPases; Phosphate; Proteins

Indexed keywords

ARGININE; GUANOSINE TRIPHOSPHATASE; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; GUANOSINE TRIPHOSPHATE; RAS PROTEIN; WATER; PHOSPHATE;

ARTICLE; CATALYSIS; COMPLEX FORMATION; CONTROLLED STUDY; ENTROPY; ESCHERICHIA COLI; INFRARED SPECTROSCOPY; MOLECULE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN HYDROLYSIS; PROTEIN INTERACTION; SIGNAL TRANSDUCTION; THERMODYNAMICS; CHEMICAL STRUCTURE; CHEMISTRY; COMPUTER SIMULATION; ENZYME ACTIVATION; ENZYME ACTIVE SITE; HYDROLYSIS; KINETICS; METABOLISM; TIME;

ARGININE; CATALYTIC DOMAIN; COMPUTER SIMULATION; ENTROPY; ENZYME ACTIVATION; HYDROLYSIS; KINETICS; MODELS, MOLECULAR; PHOSPHATES; PROTEIN CONFORMATION; RAS GTPASE-ACTIVATING PROTEINS; RAS PROTEINS; TIME FACTORS;

EID: 44049093161     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.0712095105     Document Type: Article

References (42)

1. Vetter IR, Wittinghofer A (2001) Signal transduction - The guanine nucleotide-binding switch in three dimensions. Science 294:1299-1304.
2. Wittinghofer A, Waldmann H (2000) Ras-a molecular switch involved in tumor formation. Angew Chem Int Ed 39:4192-4214.
3. Malumbres M, Barbacid M (2003) Timeline - RAS oncogenes: The first 30 years. Nat Rev Cancer 3:459-465.
4. Bos JL, Rehmann H, Wittinghofer A (2007) GEFs and GAPs: Critical elements in the control of small G proteins. Cell 129:865-877.
5. Schweins T, et al. (1995) Substrate-assisted catalysis as a mechanism for GTP hydrolysis of P21(Ras) and other GTP-binding proteins. Nat Struct Biol 2:36-44.
6. Downward J (2003) Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 3:11-22.
7. Schubbert S, Shannon K, Bollag G (2007) Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer 7:295-308.
8. Collins I, Workman P (2006) New approaches to molecular cancer therapeutics. Nat Chem Biol 2:689-700.
9. Ahmadian MR, Stege P, Scheffzek K, Wittinghofer A (1997) Confirmation of the arginine-finger hypothesis for the GAP-stimulated GTP-hydrolysis reaction of Ras. Nat Struct Biol 4:686-689.
10. Scheffzek K, et al. (1997) The Ras-RasGAP complex: Structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science 277:333-338.
11. Kosloff M, Selinger Z (2003) GTPase catalysis by Ras and other G-proteins: Insights from substrate directed superimposition. J Mol Biol 331:1157-1170.
12. Bourne HR (1997) G proteins - The arginine finger strikes again. Nature 389:673-674.
13. Egea Pascal F, et al. (2004) Substrate twinning activates the signal recognition particle and its receptor. Nature 427:215-221.
14. Focia PJ, Shepotinovskaya IV, Seidler JA, Freymann DM (2004) Heterodimeric GTPase core of the SRP targeting complex. Science 303:373-377.
15. Bowler MW, Montgomery MG, Leslie AGW, Walker JE (2007) Ground state structure of F1-ATPase from bovine heart mitochondria at 1.9 Å resolution. J Biol Chem 282:14238-14242.
16. Rittinger K, et al. (1997) Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP. Nature 388:693-697.
17. Rittinger K, Walker PA, Eccleston JF, Smerdon SJ, Gamblin SJ (1997) Structure at 1.65 angstrom of RhoA and its GTPase-activating protein in complex with a transition-state analogue. Nature 389:758-762.
18. Allin C, Ahmadian MR, Wittinghofer A, Gerwert K (2001) Monitoring the GAP catalyzed H-Ras GTPase reaction at atomic resolution in real time. Proc Natl Acad Sci USA 98:7754-7759.
19. Allin C, Gerwert K (2001) Ras catalyzes GTP hydrolysis by shifting negative charges from gamma- to beta-phosphate as revealed by time-resolved FTIR difference spectroscopy. Biochemistry 40:3037-3046.
20. Heesen Ht, Gerwert K, Schlitter J (2007) Role of the arginine finger in Ras-RasGAP revealed by QM/MM calculations. FEBS Lett 581:5677-5684.
21. Kötting C, Gerwert K (2004) Time-resolved FTIR studies provide activation free energy, activation enthalpy and activation entropy for GTPase reactions. Chem Phys 307:227-232.
22. Kötting C, et al. (2006) A phosphoryl transfer intermediate in the GTPase reaction of Ras in complex with its GTPase-activating protein. Proc Natl Acad Sci USA 103:13911-13916.
23. Chen XB, et al. (2006) A theoretical investigation of p-hydroxyphenacyl caged photo-trigger compounds: An examination of the excited state photochemistry of p-hydroxyphenacyl acetate. J Phys Chem A 110:12406-12413.
24. Pelliccioli AP, Wirz J (2002) Photoremovable protecting groups: Reaction mechanisms and applications. Photochem Photobiol Sci 1:441-458.
25. Hessling B, Souvignier G, Gerwert K (1993) A model-independent approach to assigning bacteriorhodopsin's intramolecular reactions to photocycle intermediates. Biophys J 65:1929-1941.
26. Kötting C, Kallenbach A, Suveyzdis Y, Eichholz C, Gerwert K (2007) Surface change of Ras enabling effector binding monitored in real time at atomic resolution. ChemBioChem 8:781-787.
27. Barth A, Zscherp C (2002) What vibrations tell about proteins. Q Rev Biophys 35:369-430.
28. Garczarek F, Gerwert K (2006) Functional waters in intraprotein proton transfer monitored by FTIR difference spectroscopy. Nature 439:109-112.
29. Hutson MS, Alexiev U, Shilov SV, Wise KJ, Braiman MS (2000) Evidence for a perturbation of arginine-82 in the bacteriorhodopsin photocycle from time-resolved infrared spectra. Biochemistry 39:13189-13200.
30. Warshel A, et al. (2006) Electrostatic basis for enzyme catalysis. Chem Rev 106:3210-3235.
31. Loftfield RB, Eigner EA, Pastuszyn A, Lovgren TNE, Jakubowski H (1980) Conformational-changes during enzyme catalysis - Role of water in the transition-state. Proc Natl Acad Sci USA 77:3374-3378.
32. Valentine AM, Stahl SS, Lippard SJ (1999) Mechanistic studies of the reaction of reduced methane monooxygenase hydroxylase with dioxygen and substrates. J Am Chem Soc 121:3876-3887.
33. Dunitz JD (1994) The entropic cost of bound water in crystals and biomolecules. Science 264:670.
34. Tucker J, et al. (1986) Expression of p21 proteins in Escherichia coli and stereochemistry of the nucleotide-binding site. EMBO J 5:1351-1358.
35. Ahmadian MR, Hoffmann U, Goody RS, Wittinghofer A (1997) Individual rate constants for the interaction of Ras proteins with GTPase-activating proteins determined by fluorescence spectroscopy. Biochemistry 36:4535-4541.
36. Dougherty WG, Cary SM, Parks TD (1989) Molecular genetic-analysis of a plant-virus polyprotein cleavage site - A model. Virology 171:356-364.
37. Warscheid B, et al. (November 22, 2007) Systematic approach to group-specific isotopic labeling of proteins for vibrational spectroscopy. Vib Spectrosc, 10.1016/j.vibspec.2007.11.003.
38. Park C-H, Givens RS (1997) New photoactivated protecting groups. 6. p-Hydroxyphenacyl: A phototrigger for chemical and biochemical probes. J Am Chem Soc 119:2453-2463.
39. John J, et al. (1990) Kinetics of interaction of nucleotides with nucleotide-free H-ras p21. Biochemistry 29:6058-6065.
40. Cepus V, Scheidig AJ, Goody RS, Gerwert K (1998) Time-resolved FTIR studies of the GTPase reaction of H-ras p21 reveal a key role for the β-phosphate. Biochemistry 37:10263-10271.
41. Gerwert K, Souvignier G, Hess B (1990) Simultaneous monitoring of light-induced changes in protein side-group protonation, chromophore isomerization, and backbone motion of bacteriorhodopsin by time-resolved Fourier-transform infrared spectroscopy. Proc Natl Acad Sci USA 87:9774-9778.
42. Phillips RA, Hunter JL, Eccleston JF, Webb MR (2003) The mechanism of Ras GTPase activation by neurofibromin. Biochemistry 42:3956-3965.