4B3H

Crystal structure of Mycobacterium tuberculosis fatty acid beta- oxidation complex

Summary for 4B3H

• Entry DOI: 10.2210/pdb4b3h/pdb
• Related: 4B3I 4B3J
• Descriptor: FATTY ACID BETA-OXIDATION COMPLEX ALPHA-CHAIN FADB, FATTY ACID BETA-OXIDATION COMPLEX BETA-CHAIN FADA, SULFATE ION, ... (5 entities in total)
• Functional Keywords: oxidoreductase-transferase complex, tfe, trifunctional enzyme, hetero tetramer, coa, oxidoreductase/transferase
• Biological source: MYCOBACTERIUM TUBERCULOSIS; More
• Total number of polymer chains: 4
• Total formula weight: 244643.06

Authors

Venkatesan, R.,Wierenga, R. (deposition date: 2012-07-24, release date: 2013-03-27, Last modification date: 2023-12-20)

Primary citation

Venkatesan, R.,Wierenga, R.K.
Structure of Mycobacterial Beta-Oxidation Trifunctional Enzyme Reveals its Altered Assembly and Putative Substrate Channeling Pathway.
Acs Chem.Biol., 8:1063-, 2013

PubMed Abstract: The incidence of tuberculosis is increasing due to the appearance of new drug-resistant variants. A thorough understanding of the disease organism is essential in order to create more effective drugs. In an attempt to understand better the poorly studied lipid metabolism of Mycobacterium tuberculosis (Mtb), we identified and characterized its fatty acid β-oxidation complex (trifunctional enzyme (TFE)). TFE is an α(2)β(2) complex consisting of two types of polypeptides catalyzing three of the four reactions of the β-oxidation of fatty acids. The kinetic constants (k(cat) and K(m)) show that the complexed α chain is more active than the individual α chain. Crystal structures of Mtb TFE (mtTFE) reveal that the quaternary assembly is strikingly different from the already known Pseudomonas fragi TFE (pfTFE) assembly due to the presence of a helical insertion (LA5) in the mtTFE-β subunit. This helical insertion prevents the pfTFE mode of assembly, as it would clash with helix H9A of the TFE-α chain. The mtTFE assembly appears to be more rigid and results in a different substrate channeling path between the α and the β subunits. Structural comparisons suggest that the mtTFE active sites can accommodate bulkier fatty acyl chains than in pfTFE. Although another thiolase (FadA2), more closely related to human TFE-β/thiolase, is present in the Mtb genome, it does not form a complex with mtTFE-α. Extensive phylogenetic analyses show that there are at least four TFE subfamilies. Our studies highlight the molecular properties of mtTFE, significantly extending the structural knowledge on this type of very interesting multifunctional enzymes.

PubMed: 23496842
DOI: 10.1021/CB400007K

Experimental method

X-RAY DIFFRACTION (2.3 Å)