1khr
From Proteopedia
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Crystal Structure of Vat(D) in Complex with Virginiamycin and Coenzyme A
Overview
The streptogramin class of antibiotics act to inhibit bacterial protein, synthesis, and their semisynthetic derivatives, such as, dalfopristin-quinupristin (Synercid), are used to treat serious or, life-threatening infections due to multiply antibiotic resistant bacteria., Acquired resistance of the nosocomial pathogen Enterococcus faecium to the, group A component of natural and semisynthetic streptogramin mixtures is a, prerequisite for the streptogramin resistance phenotype and is mediated by, a streptogramin acetyltransferase. The crystal structure of Vat(D), a, streptogramin acetyltransferase from a human urinary isolate of E., faecium, has been determined as an apoenzyme and in complex with either, acetyl-CoA or virginiamycin M1 and CoA. These structures illustrate the, location and arrangement of residues at the active site, and point to His, 82 as a residue that may function as a general base. The structural, similarity of Vat(D) to the xenobiotic acetyltransferase from Pseudomonas, aeruginosa indicates similarities in the catalytic mechanism for these, enzymes as well as several shared and distinctive antibiotic binding, interactions between these enzymes and their respective substrates. These, results reveal the molecular basis for a reaction by which Gram-positive, cocci acquire resistance to a last resort antibiotic.
About this Structure
1KHR is a Single protein structure of sequence from Enterococcus faecium with VIR and COA as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of Vat(D): an acetyltransferase that inactivates streptogramin group A antibiotics., Sugantino M, Roderick SL, Biochemistry. 2002 Feb 19;41(7):2209-16. PMID:11841212
Page seeded by OCA on Tue Nov 20 19:14:53 2007
