6HRD

Crystal structure of M. tuberculosis FadB2 (Rv0468)

Summary for 6HRD

• Entry DOI: 10.2210/pdb6hrd/pdb
• Descriptor: 3-hydroxybutyryl-CoA dehydrogenase, GLYCEROL (3 entities in total)
• Functional Keywords: beta-oxidation, oxidoreductase
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 6
• Total formula weight: 205585.15

Authors

Cox, J.A.G.,Besra, G.S.,Futterer, K. (deposition date: 2018-09-26, release date: 2019-01-23, Last modification date: 2024-01-24)

Primary citation

Cox, J.A.G.,Taylor, R.C.,Brown, A.K.,Attoe, S.,Besra, G.S.,Futterer, K.
Crystal structure of Mycobacterium tuberculosis FadB2 implicated in mycobacterial beta-oxidation.
Acta Crystallogr D Struct Biol, 75:101-108, 2019

PubMed Abstract: The intracellular pathogen Mycobacterium tuberculosis is the causative agent of tuberculosis, which is a leading cause of mortality worldwide. The survival of M. tuberculosis in host macrophages through long-lasting periods of persistence depends, in part, on breaking down host cell lipids as a carbon source. The critical role of fatty-acid catabolism in this organism is underscored by the extensive redundancy of the genes implicated in β-oxidation (∼100 genes). In a previous study, the enzymology of the M. tuberculosis L-3-hydroxyacyl-CoA dehydrogenase FadB2 was characterized. Here, the crystal structure of this enzyme in a ligand-free form is reported at 2.1 Å resolution. FadB2 crystallized as a dimer with three unique dimer copies per asymmetric unit. The structure of the monomer reveals a dual Rossmann-fold motif in the N-terminal domain, while the helical C-terminal domain mediates dimer formation. Comparison with the CoA- and NAD-bound human orthologue mitochondrial hydroxyacyl-CoA dehydrogenase shows extensive conservation of the residues that mediate substrate and cofactor binding. Superposition with the multi-catalytic homologue M. tuberculosis FadB, which forms a trifunctional complex with the thiolase FadA, indicates that FadB has developed structural features that prevent its self-association as a dimer. Conversely, FadB2 is unable to substitute for FadB in the tetrameric FadA-FadB complex as it lacks the N-terminal hydratase domain of FadB. Instead, FadB2 may functionally (or physically) associate with the enoyl-CoA hydratase EchA8 and the thiolases FadA2, FadA3, FadA4 or FadA6 as suggested by interrogation of the STRING protein-network database.

PubMed: 30644849
DOI: 10.1107/S2059798318017242

Experimental method

X-RAY DIFFRACTION (2.11 Å)