2WO7

Isopenicillin N synthase with substrate analogue L,L,D-ACd2Ab (unexposed)

2WO7 の概要

• エントリーDOI: 10.2210/pdb2wo7/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 2JB4 2VAU 2VBB 2VBD 2VBP 2VCM 2VE1
• 分子名称: ISOPENICILLIN N SYNTHASE, FE (II) ION, DELTA-(L-ALPHA-AMINOADIPOYL)-L-CYSTEINYL-D-VINYLGLYCINE, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, b-lactam antibiotic, metal-binding, monocyclic intermediate, oxygenase, penicillin biosynthesis
• 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: 37967.07

構造登録者

Ge, W.,Clifton, I.J.,Adlington, R.M.,Baldwin, J.E.,Rutledge, P.J. (登録日: 2009-07-22, 公開日: 2010-07-21, 最終更新日: 2024-05-08)

主引用文献

Ge, W.,Clifton, I.J.,Stok, J.E.,Adlington, R.M.,Baldwin, J.E.,Rutledge, P.J.
Crystallographic Studies on the Binding of Selectively Deuterated Lld- and Lll-Substrate Epimers by Isopenicillin N Synthase.
Biochem.Biophys.Res.Commun., 398:659-, 2010

PubMed Abstract: Isopenicillin N synthase (IPNS) is a non-heme iron(II) oxidase which catalyses the biosynthesis of isopenicillin N (IPN) from the tripeptide delta-l-alpha-aminoadipoyl-l-cysteinyl-d-valine (lld-ACV). Herein we report crystallographic studies to investigate the binding of a truncated lll-substrate in the active site of IPNS. Two epimeric tripeptides have been prepared by solution phase peptide synthesis and crystallised with the enzyme. delta-l-alpha-Aminoadipoyl-l-cysteinyl-d-2-amino-3,3-dideuteriobutyrate (lld-ACd(2)Ab) has the same configuration as the natural substrate lld-ACV at each of its three stereocentres; its epimer delta-l-alpha-aminoadipoyl-l-cysteinyl-l-2-amino-3,3-dideuteriobutyrate (lll-ACd(2)Ab) has the opposite configuration at its third amino acid. lll-ACV has previously been shown to inhibit IPNS turnover of its substrate lld-ACV; the all-protiated tripeptide delta-l-alpha-aminoadipoyl-l-cysteinyl-d-2-aminobutyrate (lld-ACAb) is a substrate for IPNS, being turned over to a mixture of penam and cepham products. Comparisons between the crystal structures of the IPNS:Fe(II):lld-ACd(2)Ab and IPNS:Fe(II):lll-ACd(2)Ab complexes offer a possible rationale for the previously observed inhibitory effects of lll-ACV on IPNS activity.

PubMed: 20603104
DOI: 10.1016/J.BBRC.2010.06.129

実験手法

X-RAY DIFFRACTION (2.5 Å)