1BK0

ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (ACV-FE COMPLEX)

1BK0 の概要

• エントリーDOI: 10.2210/pdb1bk0/pdb
• 分子名称: ISOPENICILLIN N SYNTHASE, SULFATE ION, FE (III) ION, ... (5 entities in total)
• 機能のキーワード: b-lactam antibiotic, oxygenase, penicillin biosynthesis
• 由来する生物種: Emericella nidulans
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38079.17

構造登録者

Roach, P.L.,Clifton, I.J.,Hensgens, C.M.H.,Shibata, N.,Schofield, C.J.,Hajdu, J.,Baldwin, J.E. (登録日: 1998-07-14, 公開日: 1999-01-13, 最終更新日: 2024-05-22)

主引用文献

Roach, P.L.,Clifton, I.J.,Hensgens, C.M.,Shibata, N.,Schofield, C.J.,Hajdu, J.,Baldwin, J.E.
Structure of isopenicillin N synthase complexed with substrate and the mechanism of penicillin formation.
Nature, 387:827-830, 1997

PubMed Abstract: The biosynthesis of penicillin and cephalosporin antibiotics in microorganisms requires the formation of the bicyclic nucleus of penicillin. Isopenicillin N synthase (IPNS), a non-haem iron-dependent oxidase, catalyses the reaction of a tripeptide, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV), and dioxygen to form isopenicillin N and two water molecules. Mechanistic studies suggest the reaction is initiated by ligation of the substrate thiolate to the iron centre, and proceeds through an enzyme-bound monocyclic intermediate. Here we report the crystal structure of IPNS complexed to ferrous iron and ACV, determined to 1.3 A resolution. Based on the structure, we propose a mechanism for penicillin formation that involves ligation of ACV to the iron centre, creating a vacant iron coordination site into which dioxygen can bind. Subsequently, iron-dioxygen and iron-oxo species remove the requisite hydrogens from ACV without the direct assistance of protein residues. The crystal structure of the complex with the dioxygen analogue, NO and ACV bound to the active-site iron supports this hypothesis.

PubMed: 9194566
DOI: 10.1038/42990

実験手法

X-RAY DIFFRACTION (1.3 Å)