|
|
| Line 3: |
Line 3: |
| | <StructureSection load='1uzl' size='340' side='right'caption='[[1uzl]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='1uzl' size='340' side='right'caption='[[1uzl]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1uzl]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UZL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1UZL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1uzl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UZL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UZL 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></td></tr> | + | </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></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1uzn|1uzn]], [[1uzm|1uzm]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1uzn|1uzn]], [[1uzm|1uzm]]</div></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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/3-oxoacyl-[acyl-carrier-protein]_reductase 3-oxoacyl-[acyl-carrier-protein] reductase], with EC number [https://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uzl OCA], [http://pdbe.org/1uzl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1uzl RCSB], [http://www.ebi.ac.uk/pdbsum/1uzl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1uzl ProSAT]</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=1uzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uzl OCA], [https://pdbe.org/1uzl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uzl RCSB], [https://www.ebi.ac.uk/pdbsum/1uzl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uzl ProSAT]</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/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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Structural highlights
Function
[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.[1] [2] [3]
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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
|
