Evidence for dynamics in proteins as a mechanism for ligand dissociation

Nature Chemical Biology

Volumn 8, Issue 3, 2012, Pages 246-252

  Carroll, Mary J ^a   Mauldin, Randall V ^b   Gromova, Anna V ^a   Singleton, Scott F ^a   Collins, Edward J ^b   Lee, Andrew L ^a,b  

^a UNC Hamner Institute for Drug Safety Sciences   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 DIAMINOPYRIMIDINE INHIBITOR; DIHYDROFOLATE REDUCTASE; DIHYDROFOLATE REDUCTASE INHIBITOR; LIGAND; PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; BINDING SITE; CONFORMATION; DISPERSION; DYNAMICS; LIGAND BINDING; LIGAND DISSOCIATION; MACROMOLECULE; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL;

EID: 84857190619     PISSN: 15524450     EISSN: 15524469     Source Type: Journal    
DOI: 10.1038/nchembio.769     Document Type: Article

References (37)

1. Tummino, P.J. & Copeland, R.A. Residence time of receptor-ligand complexes and its effect on biological function. Biochemistry 47, 5481-5492 (2008 (Pubitemid 351711169)
2. Lu, H. & Tonge, P.J. Drug-target residence time: critical information for lead optimization. Curr. Opin. Chem. Biol. 14, 467-474 (2010
3. Olson, J.S. & Phillips, G.N. Jr. Kinetic pathways and barriers for ligand binding to myoglobin. J. Biol. Chem. 271, 17593-17596 (1996 (Pubitemid 26250722)
4. Bourgeois, D. et al. Complex landscape of protein structural dynamics unveiled by nanosecond Laue crystallography. Proc. Natl. Acad. Sci. USA 100, 8704-8709 (2003 (Pubitemid 36899162)
5. Bourne, H.R., Sanders, D.A. & McCormick, F. The GTPase superfamily: conserved structure and molecular mechanism. Nature 349, 117-127 (1991 (Pubitemid 21912023)
6. Ishima, R., Freedberg, D.I., Wang, Y.X., Louis, J.M. & Torchia, D.A. Flap opening and dimer-interface flexibility in the free and inhibitor-bound HIV protease, and their implications for function. Structure 7, 1047-1055 (1999 (Pubitemid 29436502)
7. Eisenmesser, E.Z. et al. Intrinsic dynamics of an enzyme underlies catalysis. Nature 438, 117-121 (2005 (Pubitemid 41599831)
8. Boehr, D.D., McElheny, D., Dyson, H.J. & Wright, P.E. The dynamic energy landscape of dihydrofolate reductase catalysis. Science 313, 1638-1642 (2006 (Pubitemid 44414038)
9. Labeikovsky, W., Eisenmesser, E.Z., Bosco, D.A. & Kern, D. Structure and dynamics of pin1 during catalysis by NMR. J. Mol. Biol. 367, 1370-1381 (2007 (Pubitemid 46413270)
10. Masterson, L.R. et al. Dynamics connect substrate recognition to catalysis in protein kinase A. Nat. Chem. Biol. 6, 821-828 (2010
11. Sapienza, P.J., Mauldin, R.V. & Lee, A.L. Multi-timescale dynamics study of FKBP12 along the rapamycin-mTOR binding coordinate. J. Mol. Biol. 405, 378-394 (2010
12. Mauldin, R.V., Carroll, M.J. & Lee, A.L. Dynamic dysfunction in dihydrofolate reductase results from antifolate drug binding: modulations of dynamics within a structural state. Structure 17, 386-394 (2009
13. Carroll, M.J. et al. Direct detection of structurally resolved dynamics in a multi-conformation receptor-ligand complex. J. Am. Chem. Soc. 133, 6422-6428 (2011
14. Eisenmesser, E.Z., Bosco, D.A., Akke, M. & Kern, D. Enzyme dynamics during catalysis. Science 295, 1520-1523 (2002 (Pubitemid 34174006)
15. Zolli-Juran, M., Cechetto, J.D., Hartlen, R., Daigle, D.M. & Brown, E.D. High throughput screening identifies novel inhibitors of Escherichia coli dihydrofolate reductase that are competitive with dihydrofolate. Bioorg. Med. Chem. Lett. 13, 2493-2496 (2003 (Pubitemid 36830757)
16. Matthews, D.A. et al. Dihydrofolate reductase: X-ray structure of the binary complex with methotrexate. Science 197, 452-455 (1977
17. Sawaya, M.R. & Kraut, J. Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence. Biochemistry 36, 586-603 (1997 (Pubitemid 27057006)
18. Loria, J.P., Rance, M. & Palmer, A.G. A relaxation-compensated Carr-Purcell-Meiboom-Gill sequence for characterizing chemical exchange by NMR spectroscopy. J. Am. Chem. Soc. 121, 2331-2332 (1999 (Pubitemid 29152458)
19. Boehr, D.D., McElheny, D., Dyson, H.J. & Wright, P.E. Millisecond timescale fluctuations in dihydrofolate reductase are exquisitely sensitive to the bound ligands. Proc. Natl. Acad. Sci. USA 107, 1373-1378 (2010
20. Palmer, A.G. III, Kroenke, C.D. & Loria, J.P. Nuclear magnetic resonance methods for quantifying microsecond-to-millisecond motions in biological macromolecules. Methods Enzymol. 339, 204-238 (2001 (Pubitemid 32666562)
21. Osborne, M.J., Venkitakrishnan, R.P., Dyson, H.J. & Wright, P.E. Diagnostic chemical shift markers for loop conformation and substrate and cofactor binding in dihydrofolate reductase complexes. Protein Sci. 12, 2230-2238 (2003 (Pubitemid 37163356)
22. Mulder, F.A., Mittermaier, A., Hon, B., Dahlquist, F.W. & Kay, L.E. Studying excited states of proteins by NMR spectroscopy. Nat. Struct. Biol. 8, 932-935 (2001 (Pubitemid 33032360)
23. Baccanari, D.P. & Joyner, S.S. Dihydrofolate reductase hysteresis and its effect of inhibitor binding analyses. Biochemistry 20, 1710-1716 (1981
24. Appleman, J.R., Howell, E.E., Kraut, J., Kuhl, M. & Blakley, R.L. Role of aspartate 27 in the binding of methotrexate to dihydrofolate reductase from Escherichia coli. J. Biol. Chem. 263, 9187-9198 (1988
25. Namanja, A.T. et al. Toward flexibility-activity relationships by NMR spectroscopy: dynamics of Pin1 ligands. J. Am. Chem. Soc. 132, 5607-5609 (2010
26. Frederick, K.K., Marlow, M.S., Valentine, K.G. & Wand, A.J. Conformational entropy in molecular recognition by proteins. Nature 448, 325-329 (2007 (Pubitemid 47080342)
27. Berger, A. & Linderstrom-Lang, K. Deuterium exchange of poly-dl-alanine in aqueous solution. Arch. Biochem. Biophys. 69, 106-118 (1957
28. Hvidt, A. & Nielsen, S.O. Hydrogen exchange in proteins. Adv. Protein Chem. 21, 287-386 (1966
29. Hansen, D.F., Vallurupalli, P. & Kay, L.E. Using relaxation dispersion NMR spectroscopy to determine structures of excited, invisible protein states. J. Biomol. NMR 41, 113-120 (2008
30. Hansen, D.F., Vallurupalli, P., Lundstrom, P., Neudecker, P. & Kay, L.E. Probing chemical shifts of invisible states of proteins with relaxation dispersion NMR spectroscopy: how well can we do? J. Am. Chem. Soc. 130, 2667-2675 (2008
31. Gangjee, A., Zaveri, N., Queener, S.F. & Kisliuk, R.L. Synthesis and biological activities of tetrahydroquinazoline analogs of aminopterin and methotrexate. J. Heterocycl. Chem. 32, 243-247 (1995
32. Wider, G. & Dreier, L. Measuring protein concentrations by NMR spectroscopy. J. Am. Chem. Soc. 128, 2571-2576 (2006 (Pubitemid 43327933)
33. Delaglio, F. et al. NMRPipe: a multidimensional spectral processing system based on Unix pipes. J. Biomol. NMR 6, 277-293 (1995
34. Johnson, B.A. & Blevins, R.A. NMRView: a computer program for the visualization and analysis of NMR data. J. Biomol. NMR 4, 603-614 (1994
35. Skrynnikov, N.R., Dahlquist, F.W. & Kay, L.E. Reconstructing NMR spectra of "invisible" excited protein states using HSQC and HMQC experiments. J. Am. Chem. Soc. 124, 12352-12360 (2002 (Pubitemid 35154900)
36. Summerfield, R.L. et al. A 2.13 A structure of E. coli dihydrofolate reductase bound to a novel competitive inhibitor reveals a new binding surface involving the M20 loop region. J. Med. Chem. 49, 6977-6986 (2006 (Pubitemid 44885986)
37. Fierke, C.A., Johnson, K.A. & Benkovic, S.J. Construction and evaluation of the kinetic scheme associated with dihydrofolate reductase from Escherichia coli. Biochemistry 26, 4085-4092 (1987