View source for 6hrd


==Crystal structure of M. tuberculosis FadB2 (Rv0468)==
<StructureSection load='6hrd' size='340' side='right'caption='[[6hrd]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6hrd]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HRD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HRD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.11&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6hrd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hrd OCA], [https://pdbe.org/6hrd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hrd RCSB], [https://www.ebi.ac.uk/pdbsum/6hrd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hrd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FADB2_MYCTU FADB2_MYCTU] Catalyzes the NAD-dependent oxidation of beta-hydroxybutyryl-CoA to acetoacetyl-CoA in vitro at pH 10. Also catalyzes the reverse reaction albeit in a lower pH range of 5.5-6.5. The reverse reaction is able to use NADPH as well as NADH.<ref>PMID:20378648</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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 beta-oxidation ( approximately 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 A 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.

Crystal structure of Mycobacterium tuberculosis FadB2 implicated in mycobacterial beta-oxidation.,Cox JAG, Taylor RC, Brown AK, Attoe S, Besra GS, Futterer K Acta Crystallogr D Struct Biol. 2019 Jan 1;75(Pt 1):101-108. doi: , 10.1107/S2059798318017242. Epub 2019 Jan 8. PMID:30644849<ref>PMID:30644849</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6hrd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Besra GS]]
[[Category: Cox JAG]]
[[Category: Futterer K]]