2g5f
From Proteopedia
(New page: 200px<br /><applet load="2g5f" size="450" color="white" frame="true" align="right" spinBox="true" caption="2g5f, resolution 1.800Å" /> '''The structure of Mb...) |
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| - | [[Image:2g5f.gif|left|200px]]<br /><applet load="2g5f" size=" | + | [[Image:2g5f.gif|left|200px]]<br /><applet load="2g5f" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2g5f, resolution 1.800Å" /> | caption="2g5f, resolution 1.800Å" /> | ||
'''The structure of MbtI from Mycobacterium Tuberculosis, the first enzyme in the synthesis of Mycobactin, reveals it to be a salicylate synthase'''<br /> | '''The structure of MbtI from Mycobacterium Tuberculosis, the first enzyme in the synthesis of Mycobactin, reveals it to be a salicylate synthase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The ability to acquire iron from the extracellular environment is a key | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2G5F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with PYR, IMD and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2G5F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=PYR:'>PYR</scene>, <scene name='pdbligand=IMD:'>IMD</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G5F OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Baker, E | + | [[Category: Baker, E N.]] |
| - | [[Category: Harrison, A | + | [[Category: Harrison, A J.]] |
| - | [[Category: Lott, J | + | [[Category: Lott, J S.]] |
[[Category: Ramsay, R.]] | [[Category: Ramsay, R.]] | ||
| - | [[Category: TBSGC, TB | + | [[Category: TBSGC, TB Structural Genomics Consortium.]] |
[[Category: Yu, M.]] | [[Category: Yu, M.]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
| Line 29: | Line 29: | ||
[[Category: tbsgc]] | [[Category: tbsgc]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:28:22 2008'' |
Revision as of 15:28, 21 February 2008
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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
Overview
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.
About this Structure
2G5F is a Single protein structure of sequence from Mycobacterium tuberculosis with , and as ligands. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 17:28:22 2008
Categories: Mycobacterium tuberculosis | Single protein | Baker, E N. | Harrison, A J. | Lott, J S. | Ramsay, R. | TBSGC, TB Structural Genomics Consortium. | Yu, M. | GOL | IMD | PYR | Beta sandwhich | Protein structure initiative | Psi | Structural genomics | Tb structural genomics consortium | Tbsgc
