4UBT

Structure of the C93S variant of the 3-ketoacyl-CoA thiolase FadA5 from M. tuberculosis in complex with a steroid and CoA.

4UBT の概要

• エントリーDOI: 10.2210/pdb4ubt/pdb
• 分子名称: Acetyl-CoA acetyltransferase FadA5, COENZYME A, (2S)-2-[(8S,9S,10R,13S,14S,17R)-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propanoic acid (non-preferred name), ... (8 entities in total)
• 機能のキーワード: degradative thiolase, steroid-complex, transferase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 174370.33

構造登録者

Schaefer, C.M.,Kisker, C. (登録日: 2014-08-13, 公開日: 2014-12-17, 最終更新日: 2023-12-20)

主引用文献

Schaefer, C.M.,Lu, R.,Nesbitt, N.M.,Schiebel, J.,Sampson, N.S.,Kisker, C.
FadA5 a Thiolase from Mycobacterium tuberculosis: A Steroid-Binding Pocket Reveals the Potential for Drug Development against Tuberculosis.
Structure, 23:21-33, 2015

PubMed Abstract: With the exception of HIV, tuberculosis (TB) is the leading cause of mortality among infectious diseases. The urgent need to develop new antitubercular drugs is apparent due to the increasing number of drug-resistant Mycobacterium tuberculosis (Mtb) strains. Proteins involved in cholesterol import and metabolism have recently been discovered as potent targets against TB. FadA5, a thiolase from Mtb, is catalyzing the last step of the β-oxidation reaction of the cholesterol side-chain degradation under release of critical metabolites and was shown to be of importance during the chronic stage of TB infections. To gain structural and mechanistic insight on FadA5, we characterized the enzyme in different stages of the cleavage reaction and with a steroid bound to the binding pocket. Structural comparisons to human thiolases revealed that it should be possible to target FadA5 specifically, and the steroid-bound structure provides a solid basis for the development of inhibitors against FadA5.

PubMed: 25482540
DOI: 10.1016/j.str.2014.10.010

実験手法

X-RAY DIFFRACTION (1.7 Å)