View source for 3fig


==Crystal Structure of Leucine-bound LeuA from Mycobacterium tuberculosis==
<StructureSection load='3fig' size='340' side='right' caption='[[3fig]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3fig]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FIG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FIG FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LEU:LEUCINE'>LEU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1sr9|1sr9]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">leuA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3fig FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fig OCA], [http://pdbe.org/3fig PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fig RCSB], [http://www.ebi.ac.uk/pdbsum/3fig PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fig ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/LEU1_MYCTU LEU1_MYCTU]] Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate) (By similarity). 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fi/3fig_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3fig ConSurf].
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== Publication Abstract from PubMed ==
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.

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<ref>PMID:15159544</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3fig" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: 2-isopropylmalate synthase]]
[[Category: Baker, E N]]
[[Category: Koon, N]]
[[Category: Squire, C J]]
[[Category: Amino-acid biosynthesis]]
[[Category: Branched-chain amino acid biosynthesis]]
[[Category: Leucine biosynthesis]]
[[Category: Tim barrel]]
[[Category: Transferase]]