Work

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

Year: 1995

Type: article

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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.92.4.1172

Authors: C Fan, P C Moews, Y Shi, C T Walsh, J R Knox

Institutions: University of Connecticut, Harvard University

Language: English

Topic: Enzyme Structure and Function

Subfield: Materials Chemistry

Field: Materials Science

Domain: Physical Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases

Awards: G1235157422, D AMINOACID LIGASES AND BACTERIAL VANCOMYCIN RESISTANCE, G2863112499, Antibiotic Biosynthesis: Amino Acid Morphing