2VAT

Crystal structure of deacetylcephalosporin C acetyltransferase in complex with coenzyme A

Summary for 2VAT

• Entry DOI: 10.2210/pdb2vat/pdb
• Related: 2VAV 2VAX
• Descriptor: ACETYL-COA--DEACETYLCEPHALOSPORIN C ACETYLTRANSFERASE, COENZYME A, ACETATE ION, ... (5 entities in total)
• Functional Keywords: acetyl transferase, a/b- hydrolase fold, transferase, acyltransferase, acetyl coenzyme a, antibiotic biosynthesis, cephalosporin biosynthesis
• Biological source: ACREMONIUM CHRYSOGENUM
• Total number of polymer chains: 12
• Total formula weight: 600714.72

Authors

Lejon, S.,Ellis, J.,Valegard, K. (deposition date: 2007-09-04, release date: 2008-09-23, Last modification date: 2024-05-08)

Primary citation

Lejon, S.,Ellis, J.,Valegard, K.
The Last Step in Cephalosporin C Formation Revealed: Crystal Structures of Deacetylcephalosporin C Acetyltransferase from Acremonium Chrysogenum in Complexes with Reaction Intermediates.
J.Mol.Biol., 377:935-, 2008

PubMed Abstract: Deacetylcephalosporin C acetyltransferase (DAC-AT) catalyses the last step in the biosynthesis of cephalosporin C, a broad-spectrum beta-lactam antibiotic of large clinical importance. The acetyl transfer step has been suggested to be limiting for cephalosporin C biosynthesis, but has so far escaped detailed structural analysis. We present here the crystal structures of DAC-AT in complexes with reaction intermediates, providing crystallographic snapshots of the reaction mechanism. The enzyme is found to belong to the alpha/beta hydrolase class of acetyltransferases, and the structures support previous observations of a double displacement mechanism for the acetyl transfer reaction in other members of this class of enzymes. The structures of DAC-AT reported here provide evidence of a stable acyl-enzyme complex, thus underpinning a mechanism involving acetylation of a catalytic serine residue by acetyl coenzyme A, followed by transfer of the acetyl group to deacetylcephalosporin C through a suggested tetrahedral transition state.

PubMed: 18279889
DOI: 10.1016/J.JMB.2008.01.047

Experimental method

X-RAY DIFFRACTION (2.2 Å)