1n8w
From Proteopedia
(New page: 200px<br /><applet load="1n8w" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n8w, resolution 2.70Å" /> '''Biochemical and Stru...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1n8w.gif|left|200px]]<br /><applet load="1n8w" size=" | + | [[Image:1n8w.gif|left|200px]]<br /><applet load="1n8w" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1n8w, resolution 2.70Å" /> | caption="1n8w, resolution 2.70Å" /> | ||
'''Biochemical and Structural Studies of Malate Synthase from Mycobacterium tuberculosis'''<br /> | '''Biochemical and Structural Studies of Malate Synthase from Mycobacterium tuberculosis'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Establishment or maintenance of a persistent infection by Mycobacterium | + | Establishment or maintenance of a persistent infection by Mycobacterium tuberculosis requires the glyoxylate pathway. This is a bypass of the tricarboxylic acid cycle in which isocitrate lyase and malate synthase (GlcB) catalyze the net incorporation of carbon during growth of microorganisms on acetate or fatty acids as the primary carbon source. The glcB gene from M. tuberculosis, which encodes malate synthase, was cloned, and GlcB was expressed in Escherichia coli. The influence of media conditions on expression in M. tuberculosis indicated that this enzyme is regulated differentially to isocitrate lyase. Purified GlcB had K(m) values of 57 and 30 microm for its substrates glyoxylate and acetyl coenzyme A, respectively, and was inhibited by bromopyruvate, oxalate, and phosphoenolpyruvate. The GlcB structure was solved to 2.1-A resolution in the presence of glyoxylate and magnesium. We also report the structure of GlcB in complex with the products of the reaction, coenzyme A and malate, solved to 2.7-A resolution. Coenzyme A binds in a bent conformation, and the details of its interactions are described, together with implications on the enzyme mechanism. |
==About this Structure== | ==About this Structure== | ||
| - | 1N8W 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, SO4, MLT, COA and GLV 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:// | + | 1N8W 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=SO4:'>SO4</scene>, <scene name='pdbligand=MLT:'>MLT</scene>, <scene name='pdbligand=COA:'>COA</scene> and <scene name='pdbligand=GLV:'>GLV</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=1N8W OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bentrup, K | + | [[Category: Bentrup, K Honer zu.]] |
| - | [[Category: Huang, C | + | [[Category: Huang, C C.]] |
[[Category: Miczak, A.]] | [[Category: Miczak, A.]] | ||
| - | [[Category: Russell, D | + | [[Category: Russell, D G.]] |
| - | [[Category: Sacchettini, J | + | [[Category: Sacchettini, J C.]] |
| - | [[Category: Smith, C | + | [[Category: Smith, C V.]] |
| - | [[Category: TBSGC, TB | + | [[Category: TBSGC, TB Structural Genomics Consortium.]] |
[[Category: COA]] | [[Category: COA]] | ||
[[Category: GLV]] | [[Category: GLV]] | ||
| Line 39: | Line 39: | ||
[[Category: tbsgc]] | [[Category: tbsgc]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:03:29 2008'' |
Revision as of 12:03, 21 February 2008
|
Biochemical and Structural Studies of Malate Synthase from Mycobacterium tuberculosis
Overview
Establishment or maintenance of a persistent infection by Mycobacterium tuberculosis requires the glyoxylate pathway. This is a bypass of the tricarboxylic acid cycle in which isocitrate lyase and malate synthase (GlcB) catalyze the net incorporation of carbon during growth of microorganisms on acetate or fatty acids as the primary carbon source. The glcB gene from M. tuberculosis, which encodes malate synthase, was cloned, and GlcB was expressed in Escherichia coli. The influence of media conditions on expression in M. tuberculosis indicated that this enzyme is regulated differentially to isocitrate lyase. Purified GlcB had K(m) values of 57 and 30 microm for its substrates glyoxylate and acetyl coenzyme A, respectively, and was inhibited by bromopyruvate, oxalate, and phosphoenolpyruvate. The GlcB structure was solved to 2.1-A resolution in the presence of glyoxylate and magnesium. We also report the structure of GlcB in complex with the products of the reaction, coenzyme A and malate, solved to 2.7-A resolution. Coenzyme A binds in a bent conformation, and the details of its interactions are described, together with implications on the enzyme mechanism.
About this Structure
1N8W 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.
Reference
Biochemical and structural studies of malate synthase from Mycobacterium tuberculosis., Smith CV, Huang CC, Miczak A, Russell DG, Sacchettini JC, Honer zu Bentrup K, J Biol Chem. 2003 Jan 17;278(3):1735-43. Epub 2002 Oct 21. PMID:12393860
Page seeded by OCA on Thu Feb 21 14:03:29 2008
Categories: Malate synthase | Mycobacterium tuberculosis | Single protein | Bentrup, K Honer zu. | Huang, C C. | Miczak, A. | Russell, D G. | Sacchettini, J C. | Smith, C V. | TBSGC, TB Structural Genomics Consortium. | COA | GLV | MG | MLT | SO4 | Coenzyme a | Glcb | Glyoxylate | Glyoxylate pathway | Malate | Protein structure initiative | Psi | Structural genomics | Tb structural genomics consortium | Tbsgc
