1UOB

Deacetoxycephalosporin C synthase complexed with 2-oxoglutarate and penicillin G

Summary for 1UOB

• Entry DOI: 10.2210/pdb1uob/pdb
• Related: 1DCS 1E5H 1E5I 1HJF 1HJG 1RXF 1RXG 1UNB 1UO9 1UOF 1UOG
• Descriptor: DEACETOXYCEPHALOSPORIN C SYNTHETASE, FE (II) ION, PENICILLIN G, ... (5 entities in total)
• Functional Keywords: oxidoreductase, antibiotic biosynthesis
• Biological source: STREPTOMYCES CLAVULIGERUS
• Total number of polymer chains: 1
• Total formula weight: 35127.97

Authors

Valegard, K.,Terwisscha van Scheltinga, A.C.,Dubus, A.,Oster, L.M.,Rhangino, G.,Hajdu, J.,Andersson, I. (deposition date: 2003-09-16, release date: 2004-01-09, Last modification date: 2023-12-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.7 Å)