2gq3: Difference between revisions
New page: left|200px<br /><applet load="2gq3" size="450" color="white" frame="true" align="right" spinBox="true" caption="2gq3, resolution 2.30Å" /> '''mycobacterium tuberc... |
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[[Image:2gq3.gif|left|200px]]<br /><applet load="2gq3" size=" | [[Image:2gq3.gif|left|200px]]<br /><applet load="2gq3" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2gq3, resolution 2.30Å" /> | caption="2gq3, resolution 2.30Å" /> | ||
'''mycobacterium tuberculosis malate synthase in complex with magnesium, malate, and coenzyme A'''<br /> | '''mycobacterium tuberculosis malate synthase in complex with magnesium, malate, and coenzyme A'''<br /> | ||
==Overview== | ==Overview== | ||
Enzymes of the glyoxylate shunt have been implicated as virulence factors | Enzymes of the glyoxylate shunt have been implicated as virulence factors in several pathogenic organisms, notably Mycobacterium tuberculosis and Candida albicans. Malate synthase has thus emerged as a promising target for design of anti-microbial agents. For this effort, it is essential to have reliable models for enzyme:substrate complexes. A 2.7 Angstroms resolution crystal structure for M. tuberculosis malate synthase in the ternary complex with magnesium, malate, and coenzyme A has been previously described. However, some unusual aspects of malate and Mg(++) binding prompted an independent determination of the structure at 2.3 Angstroms resolution, in the presence of saturating concentrations of malate. The electron density map of the complex reveals the position and conformation of coenzyme A to be unchanged from that found in the previous study. However, the coordination of Mg(++) and orientation of bound malate within the active site are different. The revised position of bound malate is consistent with a reaction mechanism that does not require reorientation of the electrophilic substrate during the catalytic cycle, while the revised Mg(++) coordination is octahedral, as expected. The results should be useful in the design of malate synthase inhibitors. | ||
==About this Structure== | ==About this Structure== | ||
2GQ3 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 MG, MLT, COA and EPE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Malate_synthase Malate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.9 2.3.3.9] Full crystallographic information is available from [http:// | 2GQ3 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=MG:'>MG</scene>, <scene name='pdbligand=MLT:'>MLT</scene>, <scene name='pdbligand=COA:'>COA</scene> and <scene name='pdbligand=EPE:'>EPE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Malate_synthase Malate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.9 2.3.3.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GQ3 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Anstrom, D | [[Category: Anstrom, D M.]] | ||
[[Category: Remington, S | [[Category: Remington, S J.]] | ||
[[Category: COA]] | [[Category: COA]] | ||
[[Category: EPE]] | [[Category: EPE]] | ||
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[[Category: tim barrel]] | [[Category: tim barrel]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:34:09 2008'' | ||
Revision as of 18:34, 21 February 2008
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mycobacterium tuberculosis malate synthase in complex with magnesium, malate, and coenzyme A
OverviewOverview
Enzymes of the glyoxylate shunt have been implicated as virulence factors in several pathogenic organisms, notably Mycobacterium tuberculosis and Candida albicans. Malate synthase has thus emerged as a promising target for design of anti-microbial agents. For this effort, it is essential to have reliable models for enzyme:substrate complexes. A 2.7 Angstroms resolution crystal structure for M. tuberculosis malate synthase in the ternary complex with magnesium, malate, and coenzyme A has been previously described. However, some unusual aspects of malate and Mg(++) binding prompted an independent determination of the structure at 2.3 Angstroms resolution, in the presence of saturating concentrations of malate. The electron density map of the complex reveals the position and conformation of coenzyme A to be unchanged from that found in the previous study. However, the coordination of Mg(++) and orientation of bound malate within the active site are different. The revised position of bound malate is consistent with a reaction mechanism that does not require reorientation of the electrophilic substrate during the catalytic cycle, while the revised Mg(++) coordination is octahedral, as expected. The results should be useful in the design of malate synthase inhibitors.
About this StructureAbout this Structure
2GQ3 is a Single protein structure of sequence from Mycobacterium tuberculosis with , , and as ligands. Active as Malate synthase, with EC number 2.3.3.9 Full crystallographic information is available from OCA.
ReferenceReference
The product complex of M. tuberculosis malate synthase revisited., Anstrom DM, Remington SJ, Protein Sci. 2006 Aug;15(8):2002-7. PMID:16877713
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