2jfw: Difference between revisions

No edit summary
No edit summary
 
(23 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:2jfw.gif|left|200px]]<br />
<applet load="2jfw" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2jfw, resolution 22.&Aring;" />
'''CRYSTAL STRUCTURE OF ENTEROCOCCUS FAECIUM GLUTAMATE RACEMASE IN COMPLEX WITH TARTRATE'''<br />


==Overview==
==Crystal structure of Enterococcus faecium glutamate racemase in complex with tartrate==
Glutamate racemase is an enzyme essential to the bacterial cell wall, biosynthesis pathway, and has therefore been considered as a target for, antibacterial drug discovery. We characterized the glutamate racemases of, several pathogenic bacteria using structural and biochemical approaches., Here we describe three distinct mechanisms of regulation for the family of, glutamate racemases: allosteric activation by metabolic precursors, kinetic regulation through substrate inhibition, and D-glutamate recycling, using a d-amino acid transaminase. In a search for selective inhibitors, we identified a series of uncompetitive inhibitors specifically targeting, Helicobacter pylori glutamate racemase that bind to a cryptic allosteric, site, and used these inhibitors to probe the mechanistic and ... [[http://ispc.weizmann.ac.il/pmbin/getpm?17568739 (full description)]]
<StructureSection load='2jfw' size='340' side='right'caption='[[2jfw]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2jfw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecium Enterococcus faecium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JFW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JFW 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</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=2jfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jfw OCA], [https://pdbe.org/2jfw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jfw RCSB], [https://www.ebi.ac.uk/pdbsum/2jfw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jfw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q3XZW8_ENTFD Q3XZW8_ENTFD] Provides the (R)-glutamate required for cell wall biosynthesis.[HAMAP-Rule:MF_00258]
== 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/jf/2jfw_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=2jfw ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glutamate racemase is an enzyme essential to the bacterial cell wall biosynthesis pathway, and has therefore been considered as a target for antibacterial drug discovery. We characterized the glutamate racemases of several pathogenic bacteria using structural and biochemical approaches. Here we describe three distinct mechanisms of regulation for the family of glutamate racemases: allosteric activation by metabolic precursors, kinetic regulation through substrate inhibition, and D-glutamate recycling using a d-amino acid transaminase. In a search for selective inhibitors, we identified a series of uncompetitive inhibitors specifically targeting Helicobacter pylori glutamate racemase that bind to a cryptic allosteric site, and used these inhibitors to probe the mechanistic and dynamic features of the enzyme. These structural, kinetic and mutational studies provide insight into the physiological regulation of these essential enzymes and provide a basis for designing narrow-spectrum antimicrobial agents.


==About this Structure==
Exploitation of structural and regulatory diversity in glutamate racemases.,Lundqvist T, Fisher SL, Kern G, Folmer RH, Xue Y, Newton DT, Keating TA, Alm RA, de Jonge BL Nature. 2007 Jun 14;447(7146):817-22. PMID:17568739<ref>PMID:17568739</ref>
2JFW is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Enterococcus_faecium Enterococcus faecium]] with TLA as [[http://en.wikipedia.org/wiki/ligand ligand]]. Active as [[http://en.wikipedia.org/wiki/Glutamate_racemase Glutamate racemase]], with EC number [[http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.1.3 5.1.1.3]]. Structure known Active Site: AC1. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2JFW OCA]].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Exploitation of structural and regulatory diversity in glutamate racemases., Lundqvist T, Fisher SL, Kern G, Folmer RH, Xue Y, Newton DT, Keating TA, Alm RA, de Jonge BL, Nature. 2007 Jun 14;447(7146):817-22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17568739 17568739]
</div>
<div class="pdbe-citations 2jfw" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Glutamate racemase 3D structures|Glutamate racemase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Enterococcus faecium]]
[[Category: Enterococcus faecium]]
[[Category: Glutamate racemase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Lundqvist T]]
[[Category: Lundqvist, T.]]
[[Category: TLA]]
[[Category: glutamate racemase]]
[[Category: isomerase]]
[[Category: peptidoglycan biosynthesis]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Oct 30 11:41:18 2007''

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA