View source for 5ovl


==crystal structure of MabA bound to NADP+ from M. smegmatis==
<StructureSection load='5ovl' size='340' side='right'caption='[[5ovl]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ovl]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OVL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OVL 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=5ovl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ovl OCA], [https://pdbe.org/5ovl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ovl RCSB], [https://www.ebi.ac.uk/pdbsum/5ovl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ovl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MABA_MYCS2 MABA_MYCS2] Part of the mycobacterial fatty acid elongation system FAS-II, which is involved in mycolic acid biosynthesis (By similarity). Catalyzes the NADPH-dependent reduction of beta-ketoacyl derivatives, the second step of the FAS-II elongation cycle (By similarity). Has a preference for longer substrates (PubMed:29717709). Can use CoA derivatives as substrates in vitro (PubMed:29717709).[UniProtKB:P9WGT3]<ref>PMID:29717709</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In mycobacteria, the ketoacyl-acyl carrier protein (ACP) reductase MabA (designated FabG in other bacteria) catalyzes the NADPH-dependent reduction of beta-ketoacyl-ACP substrates to beta-hydroxyacyl-ACP products. This first reductive step in the fatty-acid biosynthesis elongation cycle is essential for bacteria, which makes MabA/FabG an interesting drug target. To date, however, very few molecules targeting FabG have been discovered and MabA remains the only enzyme of the mycobacterial type II fatty-acid synthase that lacks specific inhibitors. Despite the existence of several MabA/FabG crystal structures, the structural rearrangement that occurs upon cofactor binding is still not fully understood. Therefore, unlocking this knowledge gap could help in the design of new inhibitors. Here, high-resolution crystal structures of MabA from Mycobacterium smegmatis in its apo, NADP(+)-bound and NADPH-bound forms are reported. Comparison of these crystal structures reveals the structural reorganization of the lid region covering the active site of the enzyme. The crystal structure of the apo form revealed numerous residues that trigger steric hindrance to the binding of NADPH and substrate. Upon NADPH binding, these residues are pushed away from the active site, allowing the enzyme to adopt an open conformation. The transition from an NADPH-bound to an NADP(+)-bound form is likely to facilitate release of the product. These results may be useful for subsequent rational drug design and/or for in silico drug-screening approaches targeting MabA/FabG.

Structural rearrangements occurring upon cofactor binding in the Mycobacterium smegmatis beta-ketoacyl-acyl carrier protein reductase MabA.,Kussau T, Flipo M, Van Wyk N, Viljoen A, Olieric V, Kremer L, Blaise M Acta Crystallogr D Struct Biol. 2018 May 1;74(Pt 5):383-393. doi:, 10.1107/S2059798318002917. Epub 2018 Apr 24. PMID:29717709<ref>PMID:29717709</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ovl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-hydroxyacyl-acyl carrier protein dehydratase 3D structures|Beta-hydroxyacyl-acyl carrier protein dehydratase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycolicibacterium smegmatis MC2 155]]
[[Category: Blaise M]]
[[Category: Flipo M]]
[[Category: Kremer L]]
[[Category: Kussau T]]
[[Category: Olieric V]]
[[Category: Van Wyk N]]
[[Category: Viljoen A]]