1UNB

Deacetoxycephalosporin C synthase complexed with 2-oxoglutarate and ampicillin

1UNB の概要

• エントリーDOI: 10.2210/pdb1unb/pdb
• 関連するPDBエントリー: 1DCS 1E5H 1E5I 1HJF 1HJG 1RXF 1RXG 1UO9 1UOB 1UOF 1UOG
• 分子名称: DEACETOXYCEPHALOSPORIN C SYNTHETASE, FE (II) ION, 2-OXOGLUTARIC ACID, ... (5 entities in total)
• 機能のキーワード: oxidoreductase, antibiotic biosynthesis
• 由来する生物種: STREPTOMYCES CLAVULIGERUS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35142.99

構造登録者

Valegard, K.,Terwisscha van Scheltinga, A.C.,Dubus, A.,Oster, L.M.,Rhangino, G.,Hajdu, J.,Andersson, I. (登録日: 2003-09-09, 公開日: 2004-01-09, 最終更新日: 2023-12-13)

主引用文献

Valegard, K.,Terwisscha van Scheltinga, A.C.,Dubus, A.,Ranghino, G.,Oster, L.M.,Hajdu, J.,Andersson, I.
The Structural Basis of Cephalosporin Formation in a Mononuclear Ferrous Enzyme
Nat.Struct.Mol.Biol., 11:95-101, 2004

PubMed Abstract: Deacetoxycephalosporin-C synthase (DAOCS) is a mononuclear ferrous enzyme that transforms penicillins into cephalosporins by inserting a carbon atom into the penicillin nucleus. In the first half-reaction, dioxygen and 2-oxoglutarate produce a reactive iron-oxygen species, succinate and CO2. The oxidizing iron species subsequently reacts with penicillin to give cephalosporin and water. Here we describe high-resolution structures for ferrous DAOCS in complex with penicillins, the cephalosporin product, the cosubstrate and the coproduct. Steady-state kinetic data, quantum-chemical calculations and the new structures indicate a reaction sequence in which a 'booby-trapped' oxidizing species is formed. This species is stabilized by the negative charge of succinate on the iron. The binding sites of succinate and penicillin overlap, and when penicillin replaces succinate, it removes the stabilizing charge, eliciting oxidative attack on itself. Requisite groups of penicillin are within 1 A of the expected position of a ferryl oxygen in the enzyme-penicillin complex.

PubMed: 14718929
DOI: 10.1038/NSMB712

実験手法

X-RAY DIFFRACTION (1.5 Å)