2JB4

Isopenicillin N synthase with a 2-thiabicycloheptan-6-one product analogue

2JB4 の概要

• エントリーDOI: 10.2210/pdb2jb4/pdb
• 関連するPDBエントリー: 1BK0 1BLZ 1HB1 1HB2 1HB3 1HB4 1IPS 1OBN 1OC1 1ODM 1ODN 1QIQ 1QJE 1QJF 1UZW 1W03 1W04 1W05 1W06 1W3V 1W3X 2BJS 2BU9 2IVI 2IVJ
• 分子名称: Isopenicillin N synthase, (1S,4S,5S,7R)-7-{[(5S)-5-AMINO-5-CARBOXYPENTANOYL]AMINO}-3,3-DIMETHYL-6-OXO-2-THIABICYCLO[3.2.0]HEPTANE-4-CARBOXYLIC ACID, FE (III) ION, ... (6 entities in total)
• 機能のキーワード: antibiotic biosynthesis, penicillin biosynthesis, iron, oxygenase, vitamin c, metal-binding, oxidoreductase, b-lactam antibiotic
• 由来する生物種: Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38262.31

構造登録者

Stewart, A.C.,Clifton, I.J.,Adlington, R.M.,Baldwin, J.E.,Rutledge, P.J. (登録日: 2006-12-01, 公開日: 2007-10-16, 最終更新日: 2024-05-08)

主引用文献

Stewart, A.C.,Clifton, I.J.,Adlington, R.M.,Baldwin, J.E.,Rutledge, P.J.
A Cyclobutanone Analogue Mimics Penicillin in Binding to Isopenicillin N Synthase.
Chembiochem, 8:2003-, 2007

PubMed Abstract: A carbocyclic analogue of the beta-lactam antibiotic isopenicillin N (IPN) has been synthesised and cocrystallised with isopenicillin N synthase (IPNS), the central enzyme in the biosynthesis of penicillin antibiotics. The crystal structure of the IPNS-cyclobutanone complex reveals an active site environment similar to that seen in the enzyme-product complex generated by turnover of the natural substrate within the crystalline protein. The IPNS-cyclobutanone structure demonstrates that the product analogue is tethered to the protein by hydrogen bonding and salt bridge interactions with its carboxylate groups, as seen previously for the natural substrate and product. Furthermore, the successful cocrystallisation of this analogue with IPNS provides firm structural evidence for the utility of such cyclobutanone derivatives as hydrolytically stable analogues of bicyclic beta-lactams.

PubMed: 17907118
DOI: 10.1002/CBIC.200700176

実験手法

X-RAY DIFFRACTION (1.3 Å)