Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Feb 14;92(4):1172–1176. doi: 10.1073/pnas.92.4.1172

A common fold for peptide synthetases cleaving ATP to ADP: glutathione synthetase and D-alanine:d-alanine ligase of Escherichia coli.

C Fan 1, P C Moews 1, Y Shi 1, C T Walsh 1, J R Knox 1
PMCID: PMC42660  PMID: 7862655

Abstract

Examination of x-ray crystallographic structures shows the tertiary structure of D-alanine:D-alanine ligase (EC 6.3.2.4). a bacterial cell wall synthesizing enzyme, is similar to that of glutathione synthetase (EC 6.32.3) despite low sequence homology. Both Escherichia coli enzymes, which convert ATP to ADP during ligation to produce peptide products, are made of three domains, each folded around a 4-to 6-stranded beta-sheet core. Sandwiched between the beta-sheets of the C-terminal and central domains of each enzyme is a nonclassical ATP-binding site that contains a common set of spatially equivalent amino acids. In each enzyme, two loops are proposed to exhibit a required flexibility that allows entry of ATP and substrates, provides protection of the acylphosphate intermediate and tetrahedral adduct from hydrolysis during catalysis, and then permits release of products.

Full text

PDF
1176

Selected References

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

  1. Allison R. D. gamma-Glutamyl transpeptidase: kinetics and mechanism. Methods Enzymol. 1985;113:419–437. doi: 10.1016/s0076-6879(85)13054-5. [DOI] [PubMed] [Google Scholar]
  2. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  3. Fan C., Moews P. C., Walsh C. T., Knox J. R. Vancomycin resistance: structure of D-alanine:D-alanine ligase at 2.3 A resolution. Science. 1994 Oct 21;266(5184):439–443. doi: 10.1126/science.7939684. [DOI] [PubMed] [Google Scholar]
  4. Gushima H., Miya T., Murata K., Kimura A. Purification and characterization of glutathione synthetase from Escherichia coli B. J Appl Biochem. 1983 Jun;5(3):210–218. [PubMed] [Google Scholar]
  5. Higgins D. G., Sharp P. M. CLUSTAL: a package for performing multiple sequence alignment on a microcomputer. Gene. 1988 Dec 15;73(1):237–244. doi: 10.1016/0378-1119(88)90330-7. [DOI] [PubMed] [Google Scholar]
  6. Mengin-Lecreulx D., Flouret B., van Heijenoort J. Cytoplasmic steps of peptidoglycan synthesis in Escherichia coli. J Bacteriol. 1982 Sep;151(3):1109–1117. doi: 10.1128/jb.151.3.1109-1117.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. NEUHAUS F. C. The enzymatic synthesis of D-alanyl-D-alanine. I. Purification and properties of D-alanyl-D-alanine synthetase. J Biol Chem. 1962 Mar;237:778–786. [PubMed] [Google Scholar]
  8. Remington S. J., Matthews B. W. A general method to assess similarity of protein structures, with applications to T4 bacteriophage lysozyme. Proc Natl Acad Sci U S A. 1978 May;75(5):2180–2184. doi: 10.1073/pnas.75.5.2180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Rhee S. G., Chock P. B., Stadtman E. R. Glutamine synthetase from Escherichia coli. Methods Enzymol. 1985;113:213–241. doi: 10.1016/s0076-6879(85)13032-6. [DOI] [PubMed] [Google Scholar]
  10. Robinson A. C., Kenan D. J., Sweeney J., Donachie W. D. Further evidence for overlapping transcriptional units in an Escherichia coli cell envelope-cell division gene cluster: DNA sequence and transcriptional organization of the ddl ftsQ region. J Bacteriol. 1986 Sep;167(3):809–817. doi: 10.1128/jb.167.3.809-817.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Tanaka T., Kato H., Nishioka T., Oda J. Mutational and proteolytic studies on a flexible loop in glutathione synthetase from Escherichia coli B: the loop and arginine 233 are critical for the catalytic reaction. Biochemistry. 1992 Mar 3;31(8):2259–2265. doi: 10.1021/bi00123a007. [DOI] [PubMed] [Google Scholar]
  12. Tanaka T., Yamaguchi H., Kato H., Nishioka T., Katsube Y., Oda J. Flexibility impaired by mutations revealed the multifunctional roles of the loop in glutathione synthetase. Biochemistry. 1993 Nov 23;32(46):12398–12404. doi: 10.1021/bi00097a018. [DOI] [PubMed] [Google Scholar]
  13. Wright G. D., Walsh C. T. Identification of a common protease-sensitive region in D-alanyl-D-alanine and D-alanyl-D-lactate ligases and photoaffinity labeling with 8-azido ATP. Protein Sci. 1993 Oct;2(10):1765–1769. doi: 10.1002/pro.5560021020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Yamaguchi H., Kato H., Hata Y., Nishioka T., Kimura A., Oda J., Katsube Y. Three-dimensional structure of the glutathione synthetase from Escherichia coli B at 2.0 A resolution. J Mol Biol. 1993 Feb 20;229(4):1083–1100. doi: 10.1006/jmbi.1993.1106. [DOI] [PubMed] [Google Scholar]
  15. Yamashita M. M., Almassy R. J., Janson C. A., Cascio D., Eisenberg D. Refined atomic model of glutamine synthetase at 3.5 A resolution. J Biol Chem. 1989 Oct 25;264(30):17681–17690. doi: 10.2210/pdb2gls/pdb. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES