4OJ8

Crystal structure of carbapenem synthase in complex with (3S,5S)-carbapenam

4OJ8 の概要

• エントリーDOI: 10.2210/pdb4oj8/pdb
• 分子名称: (5R)-carbapenem-3-carboxylate synthase, FE (II) ION, 2-OXOGLUTARIC ACID, ... (6 entities in total)
• 機能のキーワード: oxidoreductase, oxygenase, iron, 2-oxoglutaric acid, antibiotic biosynthesis, carbapenam
• 由来する生物種: Pectobacterium carotovorum subsp. carotovorum
• 細胞内の位置: Cytoplasm : Q9XB59
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 102471.87

構造登録者

Boal, A.K.,Rosenzweig, A.C. (登録日: 2014-01-20, 公開日: 2014-04-02, 最終更新日: 2023-09-20)

主引用文献

Chang, W.C.,Guo, Y.,Wang, C.,Butch, S.E.,Rosenzweig, A.C.,Boal, A.K.,Krebs, C.,Bollinger, J.M.
Mechanism of the C5 stereoinversion reaction in the biosynthesis of carbapenem antibiotics.
Science, 343:1140-1144, 2014

PubMed Abstract: The bicyclic β-lactam/2-pyrrolidine precursor to all carbapenem antibiotics is biosynthesized by attachment of a carboxymethylene unit to C5 of L-proline followed by β-lactam ring closure. Carbapenem synthase (CarC), an Fe(II) and 2-(oxo)glutarate (Fe/2OG)-dependent oxygenase, then inverts the C5 configuration. Here we report the structure of CarC in complex with its substrate and biophysical dissection of its reaction to reveal the stereoinversion mechanism. An Fe(IV)-oxo intermediate abstracts the hydrogen (H•) from C5, and tyrosine 165, a residue not visualized in the published structures of CarC lacking bound substrate, donates H• to the opposite face of the resultant radical. The reaction oxidizes the Fe(II) cofactor to Fe(III), limiting wild-type CarC to one turnover, but substitution of the H•-donating tyrosine disables stereoinversion and confers to CarC the capacity for catalytic substrate oxidation.

PubMed: 24604200
DOI: 10.1126/science.1248000

実験手法

X-RAY DIFFRACTION (2.1 Å)