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| | ==The structure of MbtI from Mycobacterium Tuberculosis, the first enzyme in the synthesis of Mycobactin, reveals it to be a salicylate synthase== | | ==The structure of MbtI from Mycobacterium Tuberculosis, the first enzyme in the synthesis of Mycobactin, reveals it to be a salicylate synthase== |
| - | <StructureSection load='2g5f' size='340' side='right' caption='[[2g5f]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='2g5f' size='340' side='right'caption='[[2g5f]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2g5f]] is a 4 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=2G5F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2G5F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2g5f]] is a 4 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=2G5F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2G5F FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</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]] 1.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MbtI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</scene></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=2g5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g5f OCA], [http://pdbe.org/2g5f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2g5f RCSB], [http://www.ebi.ac.uk/pdbsum/2g5f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2g5f 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=2g5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g5f OCA], [https://pdbe.org/2g5f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2g5f RCSB], [https://www.ebi.ac.uk/pdbsum/2g5f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2g5f ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MBTI_MYCTU MBTI_MYCTU]] Mediates the production of salicylate from chorismate via an isochorismate intermediate. Presents both isochorismate synthase and isochorismate-pyruvate lyase activities. Salycilate is the starter unit in the production of the virulence-conferring salicylate-based siderophore mycobactin.<ref>PMID:16923875</ref> | + | [https://www.uniprot.org/uniprot/MBTI_MYCTU MBTI_MYCTU] Mediates the production of salicylate from chorismate via an isochorismate intermediate. Presents both isochorismate synthase and isochorismate-pyruvate lyase activities. Salycilate is the starter unit in the production of the virulence-conferring salicylate-based siderophore mycobactin.<ref>PMID:16923875</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Myctu]] | + | [[Category: Large Structures]] |
| - | [[Category: Baker, E N]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Harrison, A J]] | + | [[Category: Baker EN]] |
| - | [[Category: Lott, J S]] | + | [[Category: Harrison AJ]] |
| - | [[Category: Ramsay, R]] | + | [[Category: Lott JS]] |
| - | [[Category: Structural genomic]] | + | [[Category: Ramsay R]] |
| - | [[Category: Yu, M]] | + | [[Category: Yu M]] |
| - | [[Category: Beta sandwhich]]
| + | |
| - | [[Category: Biosynthetic protein]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Tbsgc]]
| + | |
| Structural highlights
Function
MBTI_MYCTU Mediates the production of salicylate from chorismate via an isochorismate intermediate. Presents both isochorismate synthase and isochorismate-pyruvate lyase activities. Salycilate is the starter unit in the production of the virulence-conferring salicylate-based siderophore mycobactin.[1]
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 ability to acquire iron from the extracellular environment is a key determinant of pathogenicity in mycobacteria. Mycobacterium tuberculosis acquires iron exclusively via the siderophore mycobactin T, the biosynthesis of which depends on the production of salicylate from chorismate. Salicylate production in other bacteria is either a two-step process involving an isochorismate synthase (chorismate isomerase) and a pyruvate lyase, as observed for Pseudomonas aeruginosa, or a single-step conversion catalyzed by a salicylate synthase, as with Yersinia enterocolitica. Here we present the structure of the enzyme MbtI (Rv2386c) from M. tuberculosis, solved by multiwavelength anomalous diffraction at a resolution of 1.8 A, and biochemical evidence that it is the salicylate synthase necessary for mycobactin biosynthesis. The enzyme is critically dependent on Mg2+ for activity and produces salicylate via an isochorismate intermediate. MbtI is structurally similar to salicylate synthase (Irp9) from Y. enterocolitica and the large subunit of anthranilate synthase (TrpE) and shares the overall architecture of other chorismate-utilizing enzymes, such as the related aminodeoxychorismate synthase PabB. Like Irp9, but unlike TrpE or PabB, MbtI is neither regulated by nor structurally stabilized by bound tryptophan. The structure of MbtI is the starting point for the design of inhibitors of siderophore biosynthesis, which may make useful lead compounds for the production of new antituberculosis drugs, given the strong dependence of pathogenesis on iron acquisition in M. tuberculosis.
The structure of MbtI from Mycobacterium tuberculosis, the first enzyme in the biosynthesis of the siderophore mycobactin, reveals it to be a salicylate synthase.,Harrison AJ, Yu M, Gardenborg T, Middleditch M, Ramsay RJ, Baker EN, Lott JS J Bacteriol. 2006 Sep;188(17):6081-91. PMID:16923875[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Harrison AJ, Yu M, Gardenborg T, Middleditch M, Ramsay RJ, Baker EN, Lott JS. The structure of MbtI from Mycobacterium tuberculosis, the first enzyme in the biosynthesis of the siderophore mycobactin, reveals it to be a salicylate synthase. J Bacteriol. 2006 Sep;188(17):6081-91. PMID:16923875 doi:http://dx.doi.org/188/17/6081
- ↑ Harrison AJ, Yu M, Gardenborg T, Middleditch M, Ramsay RJ, Baker EN, Lott JS. The structure of MbtI from Mycobacterium tuberculosis, the first enzyme in the biosynthesis of the siderophore mycobactin, reveals it to be a salicylate synthase. J Bacteriol. 2006 Sep;188(17):6081-91. PMID:16923875 doi:http://dx.doi.org/188/17/6081
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