View source for 3mi3


==Homocitrate Synthase Lys4 bound to Lysine==
<StructureSection load='3mi3' size='340' side='right'caption='[[3mi3]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3mi3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Schizosaccharomyces_pombe Schizosaccharomyces pombe]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3l90 3l90]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MI3 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.38&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3mi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mi3 OCA], [https://pdbe.org/3mi3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mi3 RCSB], [https://www.ebi.ac.uk/pdbsum/3mi3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mi3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HOSM_SCHPO HOSM_SCHPO] 
== 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/mi/3mi3_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=3mi3 ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
The alpha-aminoadipate pathway of lysine biosynthesis is modulated at the transcriptional and biochemical levels by feedback inhibition. The first enzyme in the alpha-aminoadipate pathway, homocitrate synthase (HCS), is the target of the feedback regulation and is strongly inhibited by l-lysine. Here we report the structure of Schizosaccharomyces pombe HCS (SpHCS) in complex with l-lysine. The structure illustrates that the amino acid directly competes with the substrate 2-oxoglutarate for binding within the active site of HCS. Differential recognition of the substrate and inhibitor is achieved via a switch position within the (alpha/beta)(8) TIM barrel of the enzyme that can distinguish between the C5-carboxylate group of 2-oxoglutarate and the epsilon-ammonium group of l-lysine. In vitro and in vivo assays demonstrate that mutations of the switch residues, which interact with the l-lysine epsilon-ammonium group, abrogate feedback inhibition, as do substitutions of residues within the C-terminal domain that were identified in a previous study of l-lysine-insensitive HCS mutants in Saccharomyces cerevisiae. Together, these results yield new insights into the mechanism of feedback regulation of an enzyme central to lysine biosynthesis.

Structural basis for L-lysine feedback inhibition of homocitrate synthase.,Bulfer SL, Scott EM, Pillus L, Trievel RC J Biol Chem. 2010 Apr 2;285(14):10446-53. Epub 2010 Jan 19. PMID:20089861<ref>PMID:20089861</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 3mi3" style="background-color:#fffaf0;"></div>

==See Also==
*[[Homocitrate synthase|Homocitrate synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Schizosaccharomyces pombe]]
[[Category: Bulfer SL]]
[[Category: Pillus L]]
[[Category: Scott EM]]
[[Category: Trievel RC]]