1KK4

Crystal Structure of Vat(D) in Complex with Acetyl-CoA

1KK4 の概要

• エントリーDOI: 10.2210/pdb1kk4/pdb
• 関連するPDBエントリー: 1KK5 1KK6
• 分子名称: STREPTOGRAMIN A ACETYLTRANSFERASE, ACETYL COENZYME *A (3 entities in total)
• 機能のキーワード: antibiotic resistance, acyltransferase, transferase
• 由来する生物種: Enterococcus faecium
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 146909.38

構造登録者

Sugantino, M.,Roderick, S.L. (登録日: 2001-12-06, 公開日: 2002-02-20, 最終更新日: 2024-02-14)

主引用文献

Sugantino, M.,Roderick, S.L.
Crystal structure of Vat(D): an acetyltransferase that inactivates streptogramin group A antibiotics.
Biochemistry, 41:2209-2216, 2002

PubMed Abstract: 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.

PubMed: 11841212
DOI: 10.1021/bi011991b

実験手法

X-RAY DIFFRACTION (2.7 Å)