Skip to main content
PMC home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1997 Sep;6(9):1849–1857. doi: 10.1002/pro.5560060905

Backbone makes a significant contribution to the electrostatics of alpha/beta-barrel proteins.

S Raychaudhuri 1, F Younas 1, P A Karplus 1, C H Faerman 1, D R Ripoll 1
PMCID: PMC2143784  PMID: 9300484

Abstract

The electrostatic properties of seven alpha/beta-barrel enzymes selected from different evolutionary families were studied: triose phosphate isomerase, fructose-1,6-bisphosphate aldolase, pyruvate kinase, mandelate racemase, trimethylamine dehydrogenase, glycolate oxidase, and narbonin, a protein without any known enzymatic activity. The backbone of the alpha/beta-barrel has a distinct electrostatic field pattern, which is dipolar along the barrel axis. When the side chains are included in the calculations the general effect is to modulate the electrostatic pattern so that the electrostatic field is generally enhanced and is focused into a specific area near the active site. We use the electrostatic flux through a square surface near the active site to gauge the functionally relevant magnitude of the electrostatic field. The calculations reveal that in six out of the seven cases the backbone itself contributes greater than 45% of the total flux. The substantial electrostatic contribution of the backbone correlates with the known preference of alpha/beta-barrel enzymes for negatively charged substrates.

Full Text

The Full Text of this article is available as a PDF (8.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antosiewicz J., McCammon J. A., Wlodek S. T., Gilson M. K. Simulation of charge-mutant acetylcholinesterases. Biochemistry. 1995 Apr 4;34(13):4211–4219. doi: 10.1021/bi00013a009. [DOI] [PubMed] [Google Scholar]
  2. Banner D. W., Bloomer A. C., Petsko G. A., Phillips D. C., Pogson C. I., Wilson I. A., Corran P. H., Furth A. J., Milman J. D., Offord R. E. Structure of chicken muscle triose phosphate isomerase determined crystallographically at 2.5 angstrom resolution using amino acid sequence data. Nature. 1975 Jun 19;255(5510):609–614. doi: 10.1038/255609a0. [DOI] [PubMed] [Google Scholar]
  3. Barber M. J., Neame P. J., Lim L. W., White S., Matthews F. S. Correlation of x-ray deduced and experimental amino acid sequences of trimethylamine dehydrogenase. J Biol Chem. 1992 Apr 5;267(10):6611–6619. [PubMed] [Google Scholar]
  4. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  5. Chothia C., Lesk A. M. The relation between the divergence of sequence and structure in proteins. EMBO J. 1986 Apr;5(4):823–826. doi: 10.1002/j.1460-2075.1986.tb04288.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Connolly M. L. Solvent-accessible surfaces of proteins and nucleic acids. Science. 1983 Aug 19;221(4612):709–713. doi: 10.1126/science.6879170. [DOI] [PubMed] [Google Scholar]
  7. Coulson A. F. A proposed structure for 'family 18' chitinases. A possible function for narbonin. FEBS Lett. 1994 Oct 31;354(1):41–44. doi: 10.1016/0014-5793(94)01084-6. [DOI] [PubMed] [Google Scholar]
  8. Farber G. K., Petsko G. A. The evolution of alpha/beta barrel enzymes. Trends Biochem Sci. 1990 Jun;15(6):228–234. doi: 10.1016/0968-0004(90)90035-a. [DOI] [PubMed] [Google Scholar]
  9. Getzoff E. D., Cabelli D. E., Fisher C. L., Parge H. E., Viezzoli M. S., Banci L., Hallewell R. A. Faster superoxide dismutase mutants designed by enhancing electrostatic guidance. Nature. 1992 Jul 23;358(6384):347–351. doi: 10.1038/358347a0. [DOI] [PubMed] [Google Scholar]
  10. Gilson M. K., Straatsma T. P., McCammon J. A., Ripoll D. R., Faerman C. H., Axelsen P. H., Silman I., Sussman J. L. Open "back door" in a molecular dynamics simulation of acetylcholinesterase. Science. 1994 Mar 4;263(5151):1276–1278. doi: 10.1126/science.8122110. [DOI] [PubMed] [Google Scholar]
  11. Hennig M., Schlesier B., Dauter Z., Pfeffer S., Betzel C., Höhne W. E., Wilson K. S. A TIM barrel protein without enzymatic activity? Crystal-structure of narbonin at 1.8 A resolution. FEBS Lett. 1992 Jul 13;306(1):80–84. doi: 10.1016/0014-5793(92)80842-5. [DOI] [PubMed] [Google Scholar]
  12. Hester G., Brenner-Holzach O., Rossi F. A., Struck-Donatz M., Winterhalter K. H., Smit J. D., Piontek K. The crystal structure of fructose-1,6-bisphosphate aldolase from Drosophila melanogaster at 2.5 A resolution. FEBS Lett. 1991 Nov 4;292(1-2):237–242. doi: 10.1016/0014-5793(91)80875-4. [DOI] [PubMed] [Google Scholar]
  13. Hol W. G., van Duijnen P. T., Berendsen H. J. The alpha-helix dipole and the properties of proteins. Nature. 1978 Jun 8;273(5662):443–446. doi: 10.1038/273443a0. [DOI] [PubMed] [Google Scholar]
  14. Klapper I., Hagstrom R., Fine R., Sharp K., Honig B. Focusing of electric fields in the active site of Cu-Zn superoxide dismutase: effects of ionic strength and amino-acid modification. Proteins. 1986 Sep;1(1):47–59. doi: 10.1002/prot.340010109. [DOI] [PubMed] [Google Scholar]
  15. Larsen T. M., Laughlin L. T., Holden H. M., Rayment I., Reed G. H. Structure of rabbit muscle pyruvate kinase complexed with Mn2+, K+, and pyruvate. Biochemistry. 1994 May 24;33(20):6301–6309. doi: 10.1021/bi00186a033. [DOI] [PubMed] [Google Scholar]
  16. Lim L. W., Mathews F. S., Steenkamp D. J. Identification of ADP in the iron-sulfur flavoprotein trimethylamine dehydrogenase. J Biol Chem. 1988 Mar 5;263(7):3075–3078. [PubMed] [Google Scholar]
  17. Lim L. W., Shamala N., Mathews F. S., Steenkamp D. J., Hamlin R., Xuong N. H. Three-dimensional structure of the iron-sulfur flavoprotein trimethylamine dehydrogenase at 2.4-A resolution. J Biol Chem. 1986 Nov 15;261(32):15140–15146. [PubMed] [Google Scholar]
  18. Lindqvist Y., Brändén C. I. The active site of spinach glycolate oxidase. J Biol Chem. 1989 Feb 25;264(6):3624–3628. [PubMed] [Google Scholar]
  19. Lindqvist Y. Refined structure of spinach glycolate oxidase at 2 A resolution. J Mol Biol. 1989 Sep 5;209(1):151–166. doi: 10.1016/0022-2836(89)90178-2. [DOI] [PubMed] [Google Scholar]
  20. Macheroux P., Kieweg V., Massey V., Söderlind E., Stenberg K., Lindqvist Y. Role of tyrosine 129 in the active site of spinach glycolate oxidase. Eur J Biochem. 1993 May 1;213(3):1047–1054. doi: 10.1111/j.1432-1033.1993.tb17852.x. [DOI] [PubMed] [Google Scholar]
  21. Malek A. A., Hy M., Honegger A., Rose K., Brenner-Holzach O. Fructose-1,6-bisphosphate aldolase from Drosophila melanogaster: primary structure analysis, secondary structure prediction, and comparison with vertebrate aldolases. Arch Biochem Biophys. 1988 Oct;266(1):10–31. doi: 10.1016/0003-9861(88)90232-9. [DOI] [PubMed] [Google Scholar]
  22. Neidhart D. J., Howell P. L., Petsko G. A., Powers V. M., Li R. S., Kenyon G. L., Gerlt J. A. Mechanism of the reaction catalyzed by mandelate racemase. 2. Crystal structure of mandelate racemase at 2.5-A resolution: identification of the active site and possible catalytic residues. Biochemistry. 1991 Sep 24;30(38):9264–9273. doi: 10.1021/bi00102a019. [DOI] [PubMed] [Google Scholar]
  23. Nicholls A., Sharp K. A., Honig B. Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins. 1991;11(4):281–296. doi: 10.1002/prot.340110407. [DOI] [PubMed] [Google Scholar]
  24. Sakon J., Adney W. S., Himmel M. E., Thomas S. R., Karplus P. A. Crystal structure of thermostable family 5 endocellulase E1 from Acidothermus cellulolyticus in complex with cellotetraose. Biochemistry. 1996 Aug 20;35(33):10648–10660. doi: 10.1021/bi9604439. [DOI] [PubMed] [Google Scholar]
  25. Schreiber G., Fersht A. R. Rapid, electrostatically assisted association of proteins. Nat Struct Biol. 1996 May;3(5):427–431. doi: 10.1038/nsb0596-427. [DOI] [PubMed] [Google Scholar]
  26. Shafferman A., Ordentlich A., Barak D., Kronman C., Ber R., Bino T., Ariel N., Osman R., Velan B. Electrostatic attraction by surface charge does not contribute to the catalytic efficiency of acetylcholinesterase. EMBO J. 1994 Aug 1;13(15):3448–3455. doi: 10.1002/j.1460-2075.1994.tb06650.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Spassov V. Z., Karshikoff A. D., Ladenstein R. Optimization of the electrostatic interactions in proteins of different functional and folding type. Protein Sci. 1994 Sep;3(9):1556–1569. doi: 10.1002/pro.5560030921. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES