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
. 1994 Apr;3(4):541–548. doi: 10.1002/pro.5560030402

A structural role for arginine in proteins: multiple hydrogen bonds to backbone carbonyl oxygens.

C L Borders Jr 1, J A Broadwater 1, P A Bekeny 1, J E Salmon 1, A S Lee 1, A M Eldridge 1, V B Pett 1
PMCID: PMC2142871  PMID: 8003972

Abstract

We propose that arginine side chains often play a previously unappreciated general structural role in the maintenance of tertiary structure in proteins, wherein the positively charged guanidinium group forms multiple hydrogen bonds to backbone carbonyl oxygens. Using as a criterion for a "structural" arginine one that forms 4 or more hydrogen bonds to 3 or more backbone carbonyl oxygens, we have used molecular graphics to locate arginines of interest in 4 proteins: Arg 180 in Thermus thermophilus manganese superoxide dismutase, Arg 254 in human carbonic anhydrase II, Arg 31 in Streptomyces rubiginosus xylose isomerase, and Arg 313 in Rhodospirillum rubrum ribulose-1,5-bisphosphate carboxylase/oxygenase. Arg 180 helps to mold the active site channel of superoxide dismutase, whereas in each of the other enzymes the structural arginine is buried in the "mantle" (i.e., inside, but near the surface) of the protein interior well removed from the active site, where it makes 5 hydrogen bonds to 4 backbone carbonyl oxygens. Using a more relaxed criterion of 3 or more hydrogen bonds to 2 or more backbone carbonyl oxygens, arginines that play a potentially important structural role were found in yeast enolase, Bacillus stearothermophilus glyceraldehyde-3-phosphate dehydrogenase, bacteriophage T4 and human lysozymes, Enteromorpha prolifera plastocyanin, HIV-1 protease, Trypanosoma brucei brucei and yeast triosephosphate isomerases, and Escherichia coli trp aporepressor (but not trp repressor or the trp repressor/operator complex).(ABSTRACT TRUNCATED AT 250 WORDS)

Full Text

The Full Text of this article is available as a PDF (792.2 KB).

Selected References

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

  1. Artymiuk P. J., Blake C. C. Refinement of human lysozyme at 1.5 A resolution analysis of non-bonded and hydrogen-bond interactions. J Mol Biol. 1981 Nov 15;152(4):737–762. doi: 10.1016/0022-2836(81)90125-x. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Bjerrum M. J. Structural and spectroscopic comparison of manganese-containing superoxide dismutases. Biochim Biophys Acta. 1987 Sep 24;915(2):225–237. doi: 10.1016/0167-4838(87)90304-9. [DOI] [PubMed] [Google Scholar]
  4. Borders C. L., Jr, Horton P. J., Beyer W. F., Jr Chemical modification of iron- and manganese-containing superoxide dismutases from Escherichia coli. Arch Biochem Biophys. 1989 Jan;268(1):74–80. doi: 10.1016/0003-9861(89)90566-3. [DOI] [PubMed] [Google Scholar]
  5. Calnan B. J., Tidor B., Biancalana S., Hudson D., Frankel A. D. Arginine-mediated RNA recognition: the arginine fork. Science. 1991 May 24;252(5009):1167–1171. doi: 10.1126/science.252.5009.1167. [DOI] [PubMed] [Google Scholar]
  6. Carrell H. L., Glusker J. P., Burger V., Manfre F., Tritsch D., Biellmann J. F. X-ray analysis of D-xylose isomerase at 1.9 A: native enzyme in complex with substrate and with a mechanism-designed inactivator. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4440–4444. doi: 10.1073/pnas.86.12.4440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chan V. W., Bjerrum M. J., Borders C. L., Jr Evidence that chemical modification of a positively charged residue at position 189 causes the loss of catalytic activity of iron-containing and manganese-containing superoxide dismutases. Arch Biochem Biophys. 1990 May 15;279(1):195–201. doi: 10.1016/0003-9861(90)90481-d. [DOI] [PubMed] [Google Scholar]
  8. Collyer C. A., Guss J. M., Sugimura Y., Yoshizaki F., Freeman H. C. Crystal structure of plastocyanin from a green alga, Enteromorpha prolifera. J Mol Biol. 1990 Feb 5;211(3):617–632. doi: 10.1016/0022-2836(90)90269-R. [DOI] [PubMed] [Google Scholar]
  9. Dauter Z., Terry H., Witzel H., Wilson K. S. Refinement of glucose isomerase from Streptomyces albus at 1.65 A with data from an imaging plate. Acta Crystallogr B. 1990 Dec 1;46(Pt 6):833–841. doi: 10.1107/s0108768190008059. [DOI] [PubMed] [Google Scholar]
  10. Dekker K., Yamagata H., Sakaguchi K., Udaka S. Xylose (glucose) isomerase gene from the thermophile Thermus thermophilus: cloning, sequencing, and comparison with other thermostable xylose isomerases. J Bacteriol. 1991 May;173(10):3078–3083. doi: 10.1128/jb.173.10.3078-3083.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dreusicke D., Karplus P. A., Schulz G. E. Refined structure of porcine cytosolic adenylate kinase at 2.1 A resolution. J Mol Biol. 1988 Jan 20;199(2):359–371. doi: 10.1016/0022-2836(88)90319-1. [DOI] [PubMed] [Google Scholar]
  12. Eriksson A. E., Jones T. A., Liljas A. Refined structure of human carbonic anhydrase II at 2.0 A resolution. Proteins. 1988;4(4):274–282. doi: 10.1002/prot.340040406. [DOI] [PubMed] [Google Scholar]
  13. Gibson J. L., Falcone D. L., Tabita F. R. Nucleotide sequence, transcriptional analysis, and expression of genes encoded within the form I CO2 fixation operon of Rhodobacter sphaeroides. J Biol Chem. 1991 Aug 5;266(22):14646–14653. [PubMed] [Google Scholar]
  14. Hartman F. C., Stringer C. D., Lee E. H. Complete primary structure of ribulosebisphosphate carboxylase/oxygenase from Rhodospirillum rubrum. Arch Biochem Biophys. 1984 Jul;232(1):280–295. doi: 10.1016/0003-9861(84)90544-7. [DOI] [PubMed] [Google Scholar]
  15. Hudson G. S., Mahon J. D., Anderson P. A., Gibbs M. J., Badger M. R., Andrews T. J., Whitfeld P. R. Comparisons of rbcL genes for the large subunit of ribulose-bisphosphate carboxylase from closely related C3 and C4 plant species. J Biol Chem. 1990 Jan 15;265(2):808–814. [PubMed] [Google Scholar]
  16. Hwang S. R., Tabita F. R. Cotranscription, deduced primary structure, and expression of the chloroplast-encoded rbcL and rbcS genes of the marine diatom Cylindrotheca sp. strain N1. J Biol Chem. 1991 Apr 5;266(10):6271–6279. [PubMed] [Google Scholar]
  17. Kannan K. K., Ramanadham M., Jones T. A. Structure, refinement, and function of carbonic anhydrase isozymes: refinement of human carbonic anhydrase I. Ann N Y Acad Sci. 1984;429:49–60. doi: 10.1111/j.1749-6632.1984.tb12314.x. [DOI] [PubMed] [Google Scholar]
  18. Lebioda L., Stec B. Mechanism of enolase: the crystal structure of enolase-Mg2(+)-2-phosphoglycerate/phosphoenolpyruvate complex at 2.2-A resolution. Biochemistry. 1991 Mar 19;30(11):2817–2822. doi: 10.1021/bi00225a012. [DOI] [PubMed] [Google Scholar]
  19. Lee C. Y., Bagdasarian M., Meng M. H., Zeikus J. G. Catalytic mechanism of xylose (glucose) isomerase from Clostridium thermosulfurogenes. Characterization of the structural gene and function of active site histidine. J Biol Chem. 1990 Nov 5;265(31):19082–19090. [PubMed] [Google Scholar]
  20. Lolis E., Alber T., Davenport R. C., Rose D., Hartman F. C., Petsko G. A. Structure of yeast triosephosphate isomerase at 1.9-A resolution. Biochemistry. 1990 Jul 17;29(28):6609–6618. doi: 10.1021/bi00480a009. [DOI] [PubMed] [Google Scholar]
  21. Ludwig M. L., Metzger A. L., Pattridge K. A., Stallings W. C. Manganese superoxide dismutase from Thermus thermophilus. A structural model refined at 1.8 A resolution. J Mol Biol. 1991 May 20;219(2):335–358. doi: 10.1016/0022-2836(91)90569-r. [DOI] [PubMed] [Google Scholar]
  22. Lundqvist T., Schneider G. Crystal structure of the ternary complex of ribulose-1,5-bisphosphate carboxylase, Mg(II), and activator CO2 at 2.3-A resolution. Biochemistry. 1991 Jan 29;30(4):904–908. doi: 10.1021/bi00218a004. [DOI] [PubMed] [Google Scholar]
  23. Matthews D. A., Bolin J. T., Burridge J. M., Filman D. J., Volz K. W., Kaufman B. T., Beddell C. R., Champness J. N., Stammers D. K., Kraut J. Refined crystal structures of Escherichia coli and chicken liver dihydrofolate reductase containing bound trimethoprim. J Biol Chem. 1985 Jan 10;260(1):381–391. [PubMed] [Google Scholar]
  24. Miller M., Schneider J., Sathyanarayana B. K., Toth M. V., Marshall G. R., Clawson L., Selk L., Kent S. B., Wlodawer A. Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 A resolution. Science. 1989 Dec 1;246(4934):1149–1152. doi: 10.1126/science.2686029. [DOI] [PubMed] [Google Scholar]
  25. Miziorko H. M., Lorimer G. H. Ribulose-1,5-bisphosphate carboxylase-oxygenase. Annu Rev Biochem. 1983;52:507–535. doi: 10.1146/annurev.bi.52.070183.002451. [DOI] [PubMed] [Google Scholar]
  26. Mrabet N. T., Van den Broeck A., Van den brande I., Stanssens P., Laroche Y., Lambeir A. M., Matthijssens G., Jenkins J., Chiadmi M., van Tilbeurgh H. Arginine residues as stabilizing elements in proteins. Biochemistry. 1992 Mar 3;31(8):2239–2253. doi: 10.1021/bi00123a005. [DOI] [PubMed] [Google Scholar]
  27. Otwinowski Z., Schevitz R. W., Zhang R. G., Lawson C. L., Joachimiak A., Marmorstein R. Q., Luisi B. F., Sigler P. B. Crystal structure of trp repressor/operator complex at atomic resolution. Nature. 1988 Sep 22;335(6188):321–329. doi: 10.1038/335321a0. [DOI] [PubMed] [Google Scholar]
  28. Phillips S. E., Schoenborn B. P. Neutron diffraction reveals oxygen-histidine hydrogen bond in oxymyoglobin. Nature. 1981 Jul 2;292(5818):81–82. doi: 10.1038/292081a0. [DOI] [PubMed] [Google Scholar]
  29. Schevitz R. W., Otwinowski Z., Joachimiak A., Lawson C. L., Sigler P. B. The three-dimensional structure of trp repressor. 1985 Oct 31-Nov 6Nature. 317(6040):782–786. doi: 10.1038/317782a0. [DOI] [PubMed] [Google Scholar]
  30. Schneider G., Lindqvist Y., Lundqvist T. Crystallographic refinement and structure of ribulose-1,5-bisphosphate carboxylase from Rhodospirillum rubrum at 1.7 A resolution. J Mol Biol. 1990 Feb 20;211(4):989–1008. doi: 10.1016/0022-2836(90)90088-4. [DOI] [PubMed] [Google Scholar]
  31. Skarzyński T., Moody P. C., Wonacott A. J. Structure of holo-glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus at 1.8 A resolution. J Mol Biol. 1987 Jan 5;193(1):171–187. doi: 10.1016/0022-2836(87)90635-8. [DOI] [PubMed] [Google Scholar]
  32. Taylor D. A., Sack J. S., Maune J. F., Beckingham K., Quiocho F. A. Structure of a recombinant calmodulin from Drosophila melanogaster refined at 2.2-A resolution. J Biol Chem. 1991 Nov 15;266(32):21375–21380. doi: 10.2210/pdb4cln/pdb. [DOI] [PubMed] [Google Scholar]
  33. Weaver L. H., Matthews B. W. Structure of bacteriophage T4 lysozyme refined at 1.7 A resolution. J Mol Biol. 1987 Jan 5;193(1):189–199. doi: 10.1016/0022-2836(87)90636-x. [DOI] [PubMed] [Google Scholar]
  34. Wierenga R. K., Noble M. E., Vriend G., Nauche S., Hol W. G. Refined 1.83 A structure of trypanosomal triosephosphate isomerase crystallized in the presence of 2.4 M-ammonium sulphate. A comparison with the structure of the trypanosomal triosephosphate isomerase-glycerol-3-phosphate complex. J Mol Biol. 1991 Aug 20;220(4):995–1015. doi: 10.1016/0022-2836(91)90368-g. [DOI] [PubMed] [Google Scholar]
  35. Wlodawer A., Deisenhofer J., Huber R. Comparison of two highly refined structures of bovine pancreatic trypsin inhibitor. J Mol Biol. 1987 Jan 5;193(1):145–156. doi: 10.1016/0022-2836(87)90633-4. [DOI] [PubMed] [Google Scholar]
  36. Wolfenden R. Waterlogged molecules. Science. 1983 Dec 9;222(4628):1087–1093. doi: 10.1126/science.6359416. [DOI] [PubMed] [Google Scholar]
  37. Zhang R. G., Joachimiak A., Lawson C. L., Schevitz R. W., Otwinowski Z., Sigler P. B. The crystal structure of trp aporepressor at 1.8 A shows how binding tryptophan enhances DNA affinity. Nature. 1987 Jun 18;327(6123):591–597. doi: 10.1038/327591a0. [DOI] [PubMed] [Google Scholar]
  38. de Vos A. M., Ultsch M., Kossiakoff A. A. Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science. 1992 Jan 17;255(5042):306–312. doi: 10.1126/science.1549776. [DOI] [PubMed] [Google Scholar]

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

RESOURCES