2VBQ

Structure of AAC(6')-Iy in complex with bisubstrate analog CoA-S- monomethyl-acetylneamine.

2VBQ の概要

• エントリーDOI: 10.2210/pdb2vbq/pdb
• 関連するPDBエントリー: 1S3Z 1S5K 1S60
• 分子名称: AMINOGLYCOSIDE 6'-N-ACETYLTRANSFERASE, (3R,9Z)-17-[(2R,3S,4R,5R,6R)-5-amino-6-{[(1R,2R,3S,4R,6S)-4,6-diamino-2,3-dihydroxycyclohexyl]oxy}-3,4-dihydroxytetrahydro-2H-pyran-2-yl]-3-hydroxy-2,2-dimethyl-4,8,15-trioxo-12-thia-5,9,16-triazaheptadec-9-en-1-yl [(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]methyl dihydrogen diphosphate, NICKEL (II) ION, ... (5 entities in total)
• 機能のキーワード: aminoglycoside, acetyltransferase, drug resistance, bisubstrate inhibitor, transferase
• 由来する生物種: SALMONELLA CHOLERAESUIS
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39548.49

構造登録者

Vetting, M.W.,Magalhaes, M.L.,Freiburger, L.,Gao, F.,Auclair, K.,Blanchard, J.S. (登録日: 2007-09-14, 公開日: 2008-01-08, 最終更新日: 2024-05-08)

主引用文献

Magalhaes, M.L.,Vetting, M.W.,Gao, F.,Freiburger, L.,Auclair, K.,Blanchard, J.S.
Kinetic and Structural Analysis of Bisubstrate Inhibition of the Salmonella Enterica Aminoglycoside 6'-N-Acetyltransferase.
Biochemistry, 47:579-, 2008

PubMed Abstract: Aminoglycosides are antibacterial compounds that act by binding to the A site of the small 30S bacterial ribosomal subunit and inhibiting protein translation. Clinical resistance to aminoglycosides is generally the result of the expression of enzymes that covalently modify the antibiotic, including phosphorylation, adenylylation, and acetylation. Bisubstrate analogs for the aminoglycoside N-acetyltransferases are nanomolar inhibitors of Enterococcus faecium AAC(6')-Ii. However, in the case of the Salmonella enterica aac(6')-Iy-encoded aminoglycoside N-acetyltransferase, we demonstrate that a series of bisubstrate analogs are only micromolar inhibitors. In contrast to studies with AAC(6')-Ii, the inhibition constants toward AAC(6')-Iy are essentially independent of both the identity of the aminoglycoside component of the bisubstrate and the number of carbon atoms that are used to link the CoA and aminoglycoside components. The patterns of inhibition suggest that the CoA portion of the bisubstrate analog can bind to the enzyme-aminoglycoside substrate complex and that the aminoglycoside portion can bind to the enzyme-CoA product complex. However, at the high concentrations of bisubstrate analog used in crystallization experiments, we could crystallize and solve the three-dimensional structure of the enzyme-bisubstrate complex. The structure reveals that both the CoA and aminoglycoside portions bind in essentially the same positions as those previously observed for the enzyme-CoA-ribostamycin complex, with only a modest adjustment to accommodate the "linker". These results are compared to previous studies of the interaction of similar bisubstrate analogs with other aminoglycoside N-acetyltransferases.

PubMed: 18095712
DOI: 10.1021/BI701957C

実験手法

X-RAY DIFFRACTION (2 Å)