Exhaustive Enumeration of the Effects of Point Charge Mutations on the Electrostatically Driven Association of Hemoglobin Subunits, Using Weighted-Ensemble Brownian Dynamics Simulations
Structural Chemistry - 2002
Tóm tắt
Electrostatic interactions between charged and otherwise polar residues in proteins, and between those residues and polar molecules nearby, are believed important in recognition of ligands, and have been investigated extensively through computer simulation. Electrostatic steering in protein dimerization was examined here by mutating each exposed surface residue of the homodimeric hemoglobin from the ark clam Scapharca inaequivalvis to the other two charge states: positive, neutral or negative. Changes in association rate coefficients observed for dimerization varied within a narrow range, from an increase of 58% for the D5N mutation to a decrease of 38% for the V91K mutation. The magnitudes of these changes were dispersed relatively uniformly within this range and mutations giving increases were similar in number to those giving decreases. Substantially more mutations inhibiting than promoting rapid association resided on the rear face of the protein as bound to its partner subunit than in other regions, indicating that the pattern of charges on the rear face strongly affects the search for the correct binding orientation. Several residues also accelerated or inhibited association for both alternative charge states, while others promoted for one and inhibited for the other, suggesting that some residue charges are optimized while others are not.
Từ khóa
Tài liệu tham khảo
Kollman, P. A., Curr. Opinion Struct. Biol. 1994, 4, 240.
McCammon, J. A., Curr. Opinion Struct. Biol. 1998, 8, 245.
Lo Conte, L.; Chothia, C.; Janin, J., J. Mol. Biol. 1999, 285, 2177.
Ermak, D. M.; McCammon, J. A., J. Chem. Phys. 1978, 69, 1352.
Brune, D.; Kim, S., Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 3835.
Brune, D.; Kim, S., Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 2930.
Antosiewicz, J.; McCammon, J. A., Biophys. J. 1995, 69, 57.
Gilson, M. K., Curr. Opinion Struct. Biol. 1995, 5, 216.
Bacquet, R. J.; McCammon, J. A.; Allison, S. A., J. Phys. Chem. 1988, 92, 7134.
Halliwell, B.; Gutteridge, J. M. C., Biochem. J. 1984, 219, 1.
Fridovich, I., Advan. Enzymol. Related Areas Mol. Biol. 1986, 58, 61.
Bannister, J. V.; Bannister, W. H.; Rotilio, G., CRC Crit. Rev. Biochem. 1987, 22, 111.
Akabas, M. H.; Karlin, A., Neuron 1995, 15, 1231.
Massoulie, J.; Pezzementi, L.; Bon, S.; Krejci, E.; Vallette, F.-M., Progr. Neurobiol. 1993, 41, 31.
Schreiber, G.; Fersht, A. R., Nature Struct. Biol. 1996, 3, 427.
Kozack, R. E.; Subramaniam, S., Protein Sci. 1993, 2, 915.
Kozack, R. E.; d'Mello, M. J.; Subramaniam, S., Biophys. J. 1995, 68, 807.
Raman, C. S.; Jemmerson, R.; Nall, B. T.; Allen, M. J., Biochemistry 1992, 31, 10370.
Fisher, E. W.; Rojnuckarin, A.; Kim, S., J. Mol. Struct. (Theochem) 2000, 529, 183.
Fisher, E. W.; Rojnuckarin, A.; Kim, S., J. Mol. Struct. (Theochem) 2001, 549, 47.
Royer, W. E., Jr., J. Mol. Biol. 1994, 235, 657.
Huber, G. A.; Kim, S., Biophys. J. 1996, 70, 97.
Rojnuckarin, A.; Kim, S.; Subramaniam, S., Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 4288.
Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E., Nucl. Acids Res. 2000, 28, 235.
Northrup, S. H.; Erickson, H. P., Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 3338.
Press, W. H.; Teukolsky, S. A.; Vetterling, W. T.; Flannery, B. P., Numerical Recipes in C, 2nd Edn.; University Press: Cambridge, 1992; p. 691.
Zhou, H.-X., J. Chem. Phys. 1998, 108, 8139.