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| - | ==MABA FROM MYCOBACTERIUM TUBERCULOSIS== | + | |
| - | <StructureSection load='1uzn' size='340' side='right' caption='[[1uzn]], [[Resolution|resolution]] 1.91Å' scene=''> | + | ==MabA from Mycobacterium tuberculosis== |
| | + | <StructureSection load='1uzn' size='340' side='right'caption='[[1uzn]], [[Resolution|resolution]] 1.91Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1uzn]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UZN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1UZN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1uzn]] is a 2 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=1UZN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UZN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CS:CESIUM+ION'>CS</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.91Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1uzl|1uzl]], [[1uzm|1uzm]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CS:CESIUM+ION'>CS</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3-oxoacyl-[acyl-carrier-protein]_reductase 3-oxoacyl-[acyl-carrier-protein] reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.100 1.1.1.100] </span></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=1uzn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uzn OCA], [https://pdbe.org/1uzn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uzn RCSB], [https://www.ebi.ac.uk/pdbsum/1uzn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uzn ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uzn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uzn OCA], [http://pdbe.org/1uzn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1uzn RCSB], [http://www.ebi.ac.uk/pdbsum/1uzn PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FABG_MYCTU FABG_MYCTU]] Catalyzes the NADPH-dependent reduction of beta-ketoacyl-ACP substrates to beta-hydroxyacyl-ACP products, the first reductive step in the elongation cycle of fatty acid biosynthesis. MabA preferentially metabolizes long-chain substrates (C8-C20) and has a poor affinity for the C4 substrate.<ref>PMID:9802011</ref> <ref>PMID:11932442</ref> <ref>PMID:19685079</ref> | + | [https://www.uniprot.org/uniprot/MABA_MYCTU MABA_MYCTU] Part of the mycobacterial fatty acid elongation system FAS-II, which is involved in mycolic acid biosynthesis (PubMed:11932442). Catalyzes the NADPH-dependent reduction of beta-ketoacyl derivatives, the second step of the FAS-II elongation cycle (PubMed:9802011, PubMed:11932442, PubMed:17059223, PubMed:18155153, PubMed:19685079). May preferentially metabolize long-chain substrates (C8-C20) (PubMed:11932442). Can use CoA derivatives as substrates in vitro (PubMed:9802011, PubMed:11932442, PubMed:17059223, PubMed:18155153).<ref>PMID:11932442</ref> <ref>PMID:17059223</ref> <ref>PMID:18155153</ref> <ref>PMID:19685079</ref> <ref>PMID:9802011</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uz/1uzn_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uz/1uzn_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | ==See Also== | | ==See Also== |
| - | *[[Beta-ketoacyl-ACP reductase|Beta-ketoacyl-ACP reductase]] | + | *[[Beta-ketoacyl carrier protein reductase 3D structures|Beta-ketoacyl carrier protein reductase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Myctu]] | + | [[Category: Large Structures]] |
| - | [[Category: Cohen-Gonsaud, M]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Ducasse, S]] | + | [[Category: Cohen-Gonsaud M]] |
| - | [[Category: Labesse, G]] | + | [[Category: Ducasse S]] |
| - | [[Category: Quemard, A]] | + | [[Category: Labesse G]] |
| - | [[Category: Beta-ketoacyl reductase]]
| + | [[Category: Quemard A]] |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
MABA_MYCTU Part of the mycobacterial fatty acid elongation system FAS-II, which is involved in mycolic acid biosynthesis (PubMed:11932442). Catalyzes the NADPH-dependent reduction of beta-ketoacyl derivatives, the second step of the FAS-II elongation cycle (PubMed:9802011, PubMed:11932442, PubMed:17059223, PubMed:18155153, PubMed:19685079). May preferentially metabolize long-chain substrates (C8-C20) (PubMed:11932442). Can use CoA derivatives as substrates in vitro (PubMed:9802011, PubMed:11932442, PubMed:17059223, PubMed:18155153).[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The fatty acid elongation system FAS-II is involved in the biosynthesis of mycolic acids, which are major and specific long-chain fatty acids of the cell envelope of Mycobacterium tuberculosis and other mycobacteria, including Mycobacterium smegmatis. The protein MabA, also named FabG1, has been shown recently to be part of FAS-II and to catalyse the NADPH-specific reduction of long chain beta-ketoacyl derivatives. This activity corresponds to the second step of an FAS-II elongation round. FAS-II is inhibited by the antituberculous drug isoniazid through the inhibition of the 2-trans-enoyl-acyl carrier protein reductase InhA. Thus, the other enzymes making up this enzymatic complex represent potential targets for designing new antituberculous drugs. The crystal structure of the apo-form MabA was solved to 2.03 A resolution by molecular replacement. MabA is tetrameric and shares the conserved fold of the short-chain dehydrogenases/reductases (SDRs). However, it exhibits some significant local rearrangements of the active-site loops in the absence of a cofactor, particularly the beta5-alpha5 region carrying the unique tryptophan residue, in agreement with previous fluorescence spectroscopy data. A similar conformation has been observed in the beta-ketoacyl reductase from Escherichia coli and the distantly related dehydratase. The distinctive enzymatic and structural properties of MabA are discussed in view of its crystal structure and that of related enzymes.
Crystal structure of MabA from Mycobacterium tuberculosis, a reductase involved in long-chain fatty acid biosynthesis.,Cohen-Gonsaud M, Ducasse S, Hoh F, Zerbib D, Labesse G, Quemard A J Mol Biol. 2002 Jul 5;320(2):249-61. PMID:12079383[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Marrakchi H, Ducasse S, Labesse G, Montrozier H, Margeat E, Emorine L, Charpentier X, Daffe M, Quemard A. MabA (FabG1), a Mycobacterium tuberculosis protein involved in the long-chain fatty acid elongation system FAS-II. Microbiology. 2002 Apr;148(Pt 4):951-60. PMID:11932442
- ↑ Silva RG, de Carvalho LP, Blanchard JS, Santos DS, Basso LA. Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein (ACP) reductase: kinetic and chemical mechanisms. Biochemistry. 2006 Oct 31;45(43):13064-73. PMID:17059223 doi:10.1021/bi0611210
- ↑ Silva RG, Rosado LA, Santos DS, Basso LA. Mycobacterium tuberculosis beta-ketoacyl-ACP reductase: alpha-secondary kinetic isotope effects and kinetic and equilibrium mechanisms of substrate binding. Arch Biochem Biophys. 2008 Mar 1;471(1):1-10. PMID:18155153 doi:10.1016/j.abb.2007.12.002
- ↑ Gurvitz A. The essential mycobacterial genes, fabG1 and fabG4, encode 3-oxoacyl-thioester reductases that are functional in yeast mitochondrial fatty acid synthase type 2. Mol Genet Genomics. 2009 Oct;282(4):407-16. Epub 2009 Aug 14. PMID:19685079 doi:http://dx.doi.org/10.1007/s00438-009-0474-2
- ↑ Banerjee A, Sugantino M, Sacchettini JC, Jacobs WR Jr. The mabA gene from the inhA operon of Mycobacterium tuberculosis encodes a 3-ketoacyl reductase that fails to confer isoniazid resistance. Microbiology. 1998 Oct;144 ( Pt 10):2697-704. PMID:9802011
- ↑ Cohen-Gonsaud M, Ducasse S, Hoh F, Zerbib D, Labesse G, Quemard A. Crystal structure of MabA from Mycobacterium tuberculosis, a reductase involved in long-chain fatty acid biosynthesis. J Mol Biol. 2002 Jul 5;320(2):249-61. PMID:12079383 doi:10.1016/S0022-2836(02)00463-1
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