1JGT

CRYSTAL STRUCTURE OF BETA-LACTAM SYNTHETASE

Summary for 1JGT

• Entry DOI: 10.2210/pdb1jgt/pdb
• Descriptor: BETA-LACTAM SYNTHETASE, MAGNESIUM ION, DIPHOSPHOMETHYLPHOSPHONIC ACID ADENOSYL ESTER, ... (6 entities in total)
• Functional Keywords: beta-lactam synthetase, asparagine synthetase, clavulanic acid, ampcpp, cea, carboxyethylarginine, hydrolase
• Biological source: Streptomyces clavuligerus
• Total number of polymer chains: 2
• Total formula weight: 111215.15

Authors

Miller, M.T.,Bachmann, B.O.,Townsend, C.A.,Rosenzweig, A.C. (deposition date: 2001-06-26, release date: 2001-12-28, Last modification date: 2024-02-07)

Primary citation

Miller, M.T.,Bachmann, B.O.,Townsend, C.A.,Rosenzweig, A.C.
Structure of beta-lactam synthetase reveals how to synthesize antibiotics instead of asparagine.
Nat.Struct.Biol., 8:684-689, 2001

PubMed Abstract: The enzyme beta-lactam synthetase (beta-LS) catalyzes the formation of the beta-lactam ring in clavulanic acid, a clinically important beta-lactamase inhibitor. Whereas the penicillin beta-lactam ring is generated by isopenicillin N synthase (IPNS) in the presence of ferrous ion and dioxygen, beta-LS uses ATP and Mg2+ as cofactors. According to sequence alignments, beta-LS is homologous to class B asparagine synthetases (AS-Bs), ATP/Mg2+-dependent enzymes that convert aspartic acid to asparagine. Here we report the first crystal structure of a beta-LS. The 1.95 A resolution structure of Streptomyces clavuligerus beta-LS provides a fully resolved view of the active site in which substrate, closely related ATP analog alpha,beta-methyleneadenosine 5'-triphosphate (AMP-CPP) and a single Mg2+ ion are present. A high degree of substrate preorganization is observed. Comparison to Escherichia coli AS-B reveals the evolutionary changes that have taken place in beta-LS that impede interdomain reaction, which is essential in AS-B, and that accommodate beta-lactam formation. The structural data provide the opportunity to alter the synthetic potential of beta-LS, perhaps leading to the creation of new beta-lactamase inhibitors and beta-lactam antibiotics.

PubMed: 11473258
DOI: 10.1038/90394

Experimental method

X-RAY DIFFRACTION (1.95 Å)