1sr9

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[[Image:1sr9.gif|left|200px]]
[[Image:1sr9.gif|left|200px]]
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{{Structure
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The line below this paragraph, containing "STRUCTURE_1sr9", creates the "Structure Box" on the page.
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|LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KIV:3-METHYL-2-OXOBUTANOIC+ACID'>KIV</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/2-isopropylmalate_synthase 2-isopropylmalate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.13 2.3.3.13] </span>
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{{STRUCTURE_1sr9| PDB=1sr9 | SCENE= }}
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1sr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sr9 OCA], [http://www.ebi.ac.uk/pdbsum/1sr9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1sr9 RCSB]</span>
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'''Crystal Structure of LeuA from Mycobacterium tuberculosis'''
'''Crystal Structure of LeuA from Mycobacterium tuberculosis'''
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[[Category: Koon, N.]]
[[Category: Koon, N.]]
[[Category: Squire, C J.]]
[[Category: Squire, C J.]]
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[[Category: tim barrel]]
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[[Category: Tim barrel]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:03:16 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:45:55 2008''
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Revision as of 06:03, 3 May 2008

Image:1sr9.gif

Template:STRUCTURE 1sr9

Crystal Structure of LeuA from Mycobacterium tuberculosis


Overview

The leucine biosynthetic pathway is essential for the growth of Mycobacterium tuberculosis and is a potential target for the design of new anti-tuberculosis drugs. The crystal structure of alpha-isopropylmalate synthase, which catalyzes the first committed step in this pathway, has been determined by multiwavelength anomalous dispersion methods and refined at 2.0-A resolution in complex with its substrate alpha-ketoisovalerate. The structure reveals a tightly associated, domain-swapped dimer in which each monomer comprises an (alpha/beta)(8) TIM barrel catalytic domain, a helical linker domain, and a regulatory domain of novel fold. Mutational and crystallographic data indicate the latter as the site for leucine feedback inhibition of activity. Domain swapping enables the linker domain of one monomer to sit over the catalytic domain of the other, inserting residues into the active site that may be important in catalysis. The alpha-ketoisovalerate substrate binds to an active site zinc ion, adjacent to a cavity that can accommodate acetyl-CoA. Sequence and structural similarities point to a catalytic mechanism similar to that of malate synthase and an evolutionary relationship with an aldolase that catalyzes the reverse reaction on a similar substrate.

About this Structure

1SR9 is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.

Reference

Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in leucine biosynthesis., Koon N, Squire CJ, Baker EN, Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8295-300. Epub 2004 May 24. PMID:15159544 Page seeded by OCA on Sat May 3 09:03:16 2008

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