4UBV

Structure of the 3-ketoacyl-CoA thiolase FadA5 from M. tuberculosis with an partially acetylated cysteine in complex with acetyl-CoA and CoA

Summary for 4UBV

• Entry DOI: 10.2210/pdb4ubv/pdb
• Descriptor: Acetyl-CoA acetyltransferase FadA5, ACETYL COENZYME *A, COENZYME A, ... (7 entities in total)
• Functional Keywords: partially acetylated degradative thiolase, acetyl-coa, coa, transferase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 2
• Total formula weight: 89048.14

Authors

Schaefer, C.M.,Kisker, C. (deposition date: 2014-08-13, release date: 2014-12-17, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.95 Å)