View source for 1ydn


==Crystal Structure of the HMG-CoA Lyase from Brucella melitensis, Northeast Structural Genomics Target LR35.==
<StructureSection load='1ydn' size='340' side='right'caption='[[1ydn]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ydn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Brucella_melitensis_bv._1_str._16M Brucella melitensis bv. 1 str. 16M]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YDN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YDN 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=1ydn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ydn OCA], [https://pdbe.org/1ydn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ydn RCSB], [https://www.ebi.ac.uk/pdbsum/1ydn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ydn ProSAT], [https://www.topsan.org/Proteins/NESGC/1ydn TOPSAN]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8YEF2_BRUME Q8YEF2_BRUME] 
== 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/yd/1ydn_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1ydn ConSurf].
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== Publication Abstract from PubMed ==
The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase catalyzes the terminal steps in ketone body generation and leucine degradation. Mutations in this enzyme cause a human autosomal recessive disorder called primary metabolic aciduria, which typically kills victims because of an inability to tolerate hypoglycemia. Here we present crystal structures of the HMG-CoA lyases from Bacillus subtilis and Brucella melitensis at 2.7 and 2.3 A resolution, respectively. These enzymes share greater than 45% sequence identity with the human orthologue. Although the enzyme has the anticipated triose-phosphate isomerase (TIM) barrel fold, the catalytic center contains a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel, contrary to the predictions of homology models. Surprisingly, the residues forming this cation-binding site and most of their interaction partners are shared with three other TIM barrel enzymes that catalyze diverse carbon-carbon bond cleavage reactions believed to proceed through enolate intermediates (4-hydroxy-2-ketovalerate aldolase, 2-isopropylmalate synthase, and transcarboxylase 5S). We propose the name "DRE-TIM metallolyases" for this newly identified enzyme family likely to employ a common catalytic reaction mechanism involving an invariant Asp-Arg-Glu (DRE) triplet. The Asp ligates the divalent cation, while the Arg probably stabilizes charge accumulation in the enolate intermediate, and the Glu maintains the precise structural alignment of the Asp and Arg. We propose a detailed model for the catalytic reaction mechanism of HMG-CoA lyase based on the examination of previously reported product complexes of other DRE-TIM metallolyases and induced fit substrate docking studies conducted using the crystal structure of human HMG-CoA lyase (reported in the accompanying paper by Fu, et al. (2006) J. Biol. Chem. 281, 7526-7532). Our model is consistent with extensive mutagenesis results and can guide subsequent studies directed at definitive experimental elucidation of this enzyme's reaction mechanism.

Crystal structures of two bacterial 3-hydroxy-3-methylglutaryl-CoA lyases suggest a common catalytic mechanism among a family of TIM barrel metalloenzymes cleaving carbon-carbon bonds.,Forouhar F, Hussain M, Farid R, Benach J, Abashidze M, Edstrom WC, Vorobiev SM, Xiao R, Acton TB, Fu Z, Kim JJ, Miziorko HM, Montelione GT, Hunt JF J Biol Chem. 2006 Mar 17;281(11):7533-45. Epub 2005 Dec 5. PMID:16330546<ref>PMID:16330546</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Brucella melitensis bv. 1 str. 16M]]
[[Category: Large Structures]]
[[Category: Abashidze M]]
[[Category: Acton TB]]
[[Category: Ciano M]]
[[Category: Forouhar F]]
[[Category: Hunt JF]]
[[Category: Hussain M]]
[[Category: Montelione GT]]
[[Category: Tong L]]
[[Category: Vorobiev SM]]
[[Category: Xiao R]]