1x9e

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /><applet load="1x9e" size="450" color="white" frame="true" align="right" spinBox="true" caption="1x9e, resolution 2.40&Aring;" /> '''Crystal structure of...)
Current revision (08:48, 14 February 2024) (edit) (undo)
 
(14 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1x9e.jpg|left|200px]]<br /><applet load="1x9e" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1x9e, resolution 2.40&Aring;" />
 
-
'''Crystal structure of HMG-CoA synthase from Enterococcus faecalis'''<br />
 
-
==Overview==
+
==Crystal structure of HMG-CoA synthase from Enterococcus faecalis==
-
Biosynthesis of the isoprenoid precursor, isopentenyl diphosphate, is a, critical function in all independently living organisms. There are two, major pathways for this synthesis, the non-mevalonate pathway found in, most eubacteria and the mevalonate pathway found in animal cells and a, number of pathogenic bacteria. An early step in this pathway is the, condensation of acetyl-CoA and acetoacetyl-CoA into HMG-CoA, catalyzed by, the enzyme HMG-CoA synthase. To explore the possibility of a small, molecule inhibitor of the enzyme functioning as a non-cell wall, antibiotic, the structure of HMG-CoA synthase from Enterococcus faecalis, (MVAS) was determined by selenomethionine MAD phasing to 2.4 A and the, enzyme complexed with its second substrate, acetoacetyl-CoA, to 1.9 A., These structures show that HMG-CoA synthase from Enterococcus is a member, of the family of thiolase fold enzymes and, while similar to the recently, published HMG-CoA synthase structures from Staphylococcus aureus, exhibit, significant differences in the structure of the C-terminal domain. The, acetoacetyl-CoA binary structure demonstrates reduced coenzyme A and, acetoacetate covalently bound to the active site cysteine through a, thioester bond. This is consistent with the kinetics of the reaction that, have shown acetoacetyl-CoA to be a potent inhibitor of the overall, reaction, and provides a starting point in the search for a small molecule, inhibitor.
+
<StructureSection load='1x9e' size='340' side='right'caption='[[1x9e]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
-
 
+
== Structural highlights ==
-
==About this Structure==
+
<table><tr><td colspan='2'>[[1x9e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X9E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1X9E FirstGlance]. <br>
-
1X9E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_synthase Hydroxymethylglutaryl-CoA synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.10 2.3.3.10] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1X9E OCA].
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-
 
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-
==Reference==
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1x9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x9e OCA], [https://pdbe.org/1x9e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1x9e RCSB], [https://www.ebi.ac.uk/pdbsum/1x9e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1x9e ProSAT]</span></td></tr>
-
X-ray crystal structures of HMG-CoA synthase from Enterococcus faecalis and a complex with its second substrate/inhibitor acetoacetyl-CoA., Steussy CN, Vartia AA, Burgner JW 2nd, Sutherlin A, Rodwell VW, Stauffacher CV, Biochemistry. 2005 Nov 1;44(43):14256-67. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16245942 16245942]
+
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/HMGCS_ENTFL HMGCS_ENTFL] Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). Functions in the mevalonate (MVA) pathway leading to isopentenyl diphosphate (IPP), a key precursor for the biosynthesis of isoprenoid compounds.<ref>PMID:12107122</ref> <ref>PMID:23794621</ref>
 +
== 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/x9/1x9e_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=1x9e ConSurf].
 +
<div style="clear:both"></div>
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Enterococcus faecalis]]
[[Category: Enterococcus faecalis]]
-
[[Category: Hydroxymethylglutaryl-CoA synthase]]
+
[[Category: Large Structures]]
-
[[Category: Single protein]]
+
[[Category: Burgner II JW]]
-
[[Category: II, J.W.Burgner.]]
+
[[Category: Rodwell VW]]
-
[[Category: Rodwell, V.W.]]
+
[[Category: Stauffacher CV]]
-
[[Category: Stauffacher, C.V.]]
+
[[Category: Steussy CN]]
-
[[Category: Steussy, C.N.]]
+
[[Category: Sutherlin A]]
-
[[Category: Sutherlin, A.]]
+
[[Category: Vartia AA]]
-
[[Category: Vartia, A.A.]]
+
-
[[Category: SO4]]
+
-
[[Category: thiolase family]]
+
-
 
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 01:42:12 2007''
+

Current revision

Crystal structure of HMG-CoA synthase from Enterococcus faecalis

PDB ID 1x9e

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1x9e"
Personal tools