1f8m
From Proteopedia
(New page: 200px<br /><applet load="1f8m" size="450" color="white" frame="true" align="right" spinBox="true" caption="1f8m, resolution 1.80Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1f8m.gif|left|200px]]<br /><applet load="1f8m" size=" | + | [[Image:1f8m.gif|left|200px]]<br /><applet load="1f8m" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1f8m, resolution 1.80Å" /> | caption="1f8m, resolution 1.80Å" /> | ||
'''CRYSTAL STRUCTURE OF 3-BROMOPYRUVATE MODIFIED ISOCITRATE LYASE (ICL) FROM MYCOBACTERIUM TUBERCULOSIS'''<br /> | '''CRYSTAL STRUCTURE OF 3-BROMOPYRUVATE MODIFIED ISOCITRATE LYASE (ICL) FROM MYCOBACTERIUM TUBERCULOSIS'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Isocitrate lyase (ICL) plays a pivotal role in the persistence of | + | Isocitrate lyase (ICL) plays a pivotal role in the persistence of Mycobacterium tuberculosis in mice by sustaining intracellular infection in inflammatory macrophages. The enzyme allows net carbon gain by diverting acetyl-CoA from beta-oxidation of fatty acids into the glyoxylate shunt pathway. Given its potential as a drug target against persistent infections, we solved its structure without ligand and in complex with two inhibitors. Covalent modification of an active site residue, Cys 191, by the inhibitor 3-bromopyruvate traps the enzyme in a catalytic conformation with the active site completely inaccessible to solvent. The structure of a C191S mutant of the enzyme with the inhibitor 3-nitropropionate provides further insight into the reaction mechanism. |
==About this Structure== | ==About this Structure== | ||
| - | 1F8M 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 and PYR as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Isocitrate_lyase Isocitrate lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.1 4.1.3.1] Full crystallographic information is available from [http:// | + | 1F8M 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> and <scene name='pdbligand=PYR:'>PYR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Isocitrate_lyase Isocitrate lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.1 4.1.3.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F8M OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bentrup, K | + | [[Category: Bentrup, K Hoener zu.]] |
| - | [[Category: Jr., W | + | [[Category: Jr., W R.Jacobs.]] |
| - | [[Category: McKinney, J | + | [[Category: McKinney, J D.]] |
| - | [[Category: Russell, D | + | [[Category: Russell, D G.]] |
| - | [[Category: Sacchettini, J | + | [[Category: Sacchettini, J C.]] |
[[Category: Sharma, S.]] | [[Category: Sharma, S.]] | ||
[[Category: Sharma, V.]] | [[Category: Sharma, V.]] | ||
| - | [[Category: TBSGC, TB | + | [[Category: TBSGC, TB Structural Genomics Consortium.]] |
[[Category: MG]] | [[Category: MG]] | ||
[[Category: PYR]] | [[Category: PYR]] | ||
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[[Category: tbsgc]] | [[Category: tbsgc]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:36:03 2008'' |
Revision as of 10:36, 21 February 2008
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CRYSTAL STRUCTURE OF 3-BROMOPYRUVATE MODIFIED ISOCITRATE LYASE (ICL) FROM MYCOBACTERIUM TUBERCULOSIS
Overview
Isocitrate lyase (ICL) plays a pivotal role in the persistence of Mycobacterium tuberculosis in mice by sustaining intracellular infection in inflammatory macrophages. The enzyme allows net carbon gain by diverting acetyl-CoA from beta-oxidation of fatty acids into the glyoxylate shunt pathway. Given its potential as a drug target against persistent infections, we solved its structure without ligand and in complex with two inhibitors. Covalent modification of an active site residue, Cys 191, by the inhibitor 3-bromopyruvate traps the enzyme in a catalytic conformation with the active site completely inaccessible to solvent. The structure of a C191S mutant of the enzyme with the inhibitor 3-nitropropionate provides further insight into the reaction mechanism.
About this Structure
1F8M is a Single protein structure of sequence from Mycobacterium tuberculosis with and as ligands. Active as Isocitrate lyase, with EC number 4.1.3.1 Full crystallographic information is available from OCA.
Reference
Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis., Sharma V, Sharma S, Hoener zu Bentrup K, McKinney JD, Russell DG, Jacobs WR Jr, Sacchettini JC, Nat Struct Biol. 2000 Aug;7(8):663-8. PMID:10932251
Page seeded by OCA on Thu Feb 21 12:36:03 2008
Categories: Isocitrate lyase | Mycobacterium tuberculosis | Single protein | Bentrup, K Hoener zu. | Jr., W R.Jacobs. | McKinney, J D. | Russell, D G. | Sacchettini, J C. | Sharma, S. | Sharma, V. | TBSGC, TB Structural Genomics Consortium. | MG | PYR | Alpha-beta barrel | Bromopyuvate modification | Closed conformation | Helix-swapping | Protein structure initiative | Psi | Structural genomics | Tb structural genomics consortium | Tbsgc
