|Gene:||bls||Accession Number: G-10269 (MetaCyc)|
Synonyms: bls2, orf3
Species: Streptomyces clavuligerus
Recombinant β-lactam synthetase expressed in Escherichia coli has been purified. It was homogeneous by SDS-PAGE, although its experimentally detrmined molecular mass and subunit structure were not reported [Bachmann00]. The crystal structure of the enzyme has been reported [Miller01a].
Molecular Weight of Polypeptide: 54.53 kD (from nucleotide sequence)
Relationship Links: Entrez-Nucleotide:RELATED-TO:U87786 , InterPro:IN-FAMILY:IPR000583 , InterPro:IN-FAMILY:IPR001962 , InterPro:IN-FAMILY:IPR014729 , InterPro:IN-FAMILY:IPR029055 , PDB:Structure:1jgt , PDB:Structure:1M1Z , PDB:Structure:1MB9 , PDB:Structure:1MBZ , PDB:Structure:1MC1 , Pfam:IN-FAMILY:PF00733 , Pfam:IN-FAMILY:PF13537
Enzymatic reaction of: β-lactam synthetase
Synonyms: (carboxyethyl)arginine β-lactam synthase, β-LS
EC Number: 22.214.171.124
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.
The reaction is physiologically favored in the direction shown.
In Pathways: clavulanate biosynthesis
β-Lactam synthetase converts the β-amino acid N2-(2-carboxyethyl)-L-arginine to the monocyclic β-lactam deoxyamidinoproclavaminate (deoxyguanidinoproclavaminate). This ATP and Mg2+-dependent enzyme catalyzes the intramolecular closure of the β-lactam ring in deoxyamidinoproclavaminate. A catalytic mechanism involving adenylation of N2-(2-carboxyethyl)-L-arginine followed by closure of the β-lactam ring has been proposed [Bachmann00, Miller02d].
Product inhibition of the enzyme was demonstrated. Deoxyamidinoproclavaminate (deoxyguanidinoproclavaminate) and diphosphate showed competitive and noncompetitive inhibition respectively when N2-(2-carboxyethyl)-L-arginine was the variable substrate. Deoxyamidinoproclavaminate (deoxyguanidinoproclavaminate) and diphosphate showed noncompetitive and competitive inhibition respectively when ATP was the variable substrate [Bachmann00].
Jensen04: Jensen SE, Paradkar AS, Mosher RH, Anders C, Beatty PH, Brumlik MJ, Griffin A, Barton B (2004). "Five additional genes are involved in clavulanic acid biosynthesis in Streptomyces clavuligerus." Antimicrob Agents Chemother 48(1);192-202. PMID: 14693539
Miller01a: Miller MT, Bachmann BO, Townsend CA, Rosenzweig AC (2001). "Structure of beta-lactam synthetase reveals how to synthesize antibiotics instead of asparagine." Nat Struct Biol 8(8);684-9. PMID: 11473258
Miller02d: Miller MT, Bachmann BO, Townsend CA, Rosenzweig AC (2002). "The catalytic cycle of beta -lactam synthetase observed by x-ray crystallographic snapshots." Proc Natl Acad Sci U S A 99(23);14752-7. PMID: 12409610
Tahlan04: Tahlan K, Park HU, Wong A, Beatty PH, Jensen SE (2004). "Two sets of paralogous genes encode the enzymes involved in the early stages of clavulanic acid and clavam metabolite biosynthesis in Streptomyces clavuligerus." Antimicrob Agents Chemother 48(3);930-9. PMID: 14982786
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