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| | ==Crystal structure of MabA-C60V/G139A/S144L== | | ==Crystal structure of MabA-C60V/G139A/S144L== |
| - | <StructureSection load='2ntn' size='340' side='right' caption='[[2ntn]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='2ntn' size='340' side='right'caption='[[2ntn]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ntn]] 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=2NTN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2NTN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ntn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NTN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NTN FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1uzl|1uzl]], [[1uzm|1uzm]], [[1uzn|1uzn]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1uzl|1uzl]], [[1uzm|1uzm]], [[1uzn|1uzn]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fabG, fabG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fabG, fabG1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=2ntn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ntn OCA], [http://pdbe.org/2ntn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ntn RCSB], [http://www.ebi.ac.uk/pdbsum/2ntn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ntn 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=2ntn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ntn OCA], [https://pdbe.org/2ntn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ntn RCSB], [https://www.ebi.ac.uk/pdbsum/2ntn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ntn 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]] |
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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: Large Structures]] |
| | [[Category: Myctu]] | | [[Category: Myctu]] |
| | [[Category: Cohen-Gonsaud, M]] | | [[Category: Cohen-Gonsaud, M]] |
| 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 MabA protein from Mycobacterium tuberculosis is a validated drug target. Previous structural studies of this protein showed dynamic behaviour in the catalytic site and described motion between an open 'active' holo form (with NADP) and a closed 'inactive' apo form (without NADP). Here, a mutation (G139A) is reported that leads to complete protein inactivation and freezes the catalytic site into its closed form, even in the presence of the cofactor. This observation suggests a new way to develop anti-MabA drugs via protein stabilization of the 'inactive' form.
Lack of dynamics in the MabA active site kills the enzyme activity: practical consequences for drug-design studies.,Poncet-Montange G, Ducasse-Cabanot S, Quemard A, Labesse G, Cohen-Gonsaud M Acta Crystallogr D Biol Crystallogr. 2007 Aug;63(Pt 8):923-5. Epub 2007, Jul 17. PMID:17642518[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
- ↑ Poncet-Montange G, Ducasse-Cabanot S, Quemard A, Labesse G, Cohen-Gonsaud M. Lack of dynamics in the MabA active site kills the enzyme activity: practical consequences for drug-design studies. Acta Crystallogr D Biol Crystallogr. 2007 Aug;63(Pt 8):923-5. Epub 2007, Jul 17. PMID:17642518 doi:10.1107/S0907444907024158
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