1ENY

CRYSTAL STRUCTURE AND FUNCTION OF THE ISONIAZID TARGET OF MYCOBACTERIUM TUBERCULOSIS

1ENY の概要

• エントリーDOI: 10.2210/pdb1eny/pdb
• 分子名称: ENOYL-ACYL CARRIER PROTEIN (ACP) REDUCTASE, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: structural genomics, psi, protein structure initiative, tb structural genomics consortium, tbsgc, oxidoreductase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29056.99

構造登録者

Dessen, A.,Quemard, A.,Blanchard, J.S.,Jacobs Jr., W.R.,Sacchettini, J.C.,TB Structural Genomics Consortium (TBSGC) (登録日: 1995-01-27, 公開日: 1996-01-29, 最終更新日: 2024-02-07)

主引用文献

Dessen, A.,Quemard, A.,Blanchard, J.S.,Jacobs Jr., W.R.,Sacchettini, J.C.
Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis.
Science, 267:1638-1641, 1995

PubMed Abstract: Resistance to isoniazid in Mycobacterium tuberculosis can be mediated by substitution of alanine for serine 94 in the InhA protein, the drug's primary target. InhA was shown to catalyze the beta-nicotinamide adenine dinucleotide (NADH)-specific reduction of 2-trans-enoyl-acyl carrier protein, an essential step in fatty acid elongation. Kinetic analyses suggested that isoniazid resistance is due to a decreased affinity of the mutant protein for NADH. The three-dimensional structures of wild-type and mutant InhA, refined to 2.2 and 2.7 angstroms, respectively, revealed that drug resistance is directly related to a perturbation in the hydrogen-bonding network that stabilizes NADH binding.

PubMed: 7886450

実験手法

X-RAY DIFFRACTION (2.2 Å)