1f8i
From Proteopedia
(New page: 200px<br /><applet load="1f8i" size="450" color="white" frame="true" align="right" spinBox="true" caption="1f8i, resolution 2.25Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1f8i.gif|left|200px]]<br /><applet load="1f8i" size=" | + | [[Image:1f8i.gif|left|200px]]<br /><applet load="1f8i" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1f8i, resolution 2.25Å" /> | caption="1f8i, resolution 2.25Å" /> | ||
'''CRYSTAL STRUCTURE OF ISOCITRATE LYASE:NITROPROPIONATE:GLYOXYLATE COMPLEX FROM MYCOBACTERIUM TUBERCULOSIS'''<br /> | '''CRYSTAL STRUCTURE OF ISOCITRATE LYASE:NITROPROPIONATE:GLYOXYLATE COMPLEX 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== | ||
| - | 1F8I 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, GLV and SIN 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:// | + | 1F8I 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=GLV:'>GLV</scene> and <scene name='pdbligand=SIN:'>SIN</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=1F8I 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: GLV]] | [[Category: GLV]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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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 12:35:59 2008'' |
Revision as of 10:36, 21 February 2008
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CRYSTAL STRUCTURE OF ISOCITRATE LYASE:NITROPROPIONATE:GLYOXYLATE COMPLEX 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
1F8I 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 12:35:59 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. | GLV | MG | SIN | Alpha-beta barrel | Closed conformation | Protein structure initiative | Psi | Structural genomics | Swapped helices | Tb structural genomics consortium | Tbsgc
