2oho: Difference between revisions
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< | ==Structural Basis for Glutamate Racemase Inhibitor== | ||
<StructureSection load='2oho' size='340' side='right'caption='[[2oho]], [[Resolution|resolution]] 2.25Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2oho]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pyogenes_M1_GAS Streptococcus pyogenes M1 GAS]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OHO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OHO 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]] 2.25Å</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> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2oho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oho OCA], [https://pdbe.org/2oho PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oho RCSB], [https://www.ebi.ac.uk/pdbsum/2oho PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oho ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MURI_STRP1 MURI_STRP1] Provides the (R)-glutamate required for cell wall biosynthesis (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/oh/2oho_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=2oho ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
D-Glutamic acid is a required biosynthetic building block for peptidoglycan, and the enzyme glutamate racemase (GluR) catalyzes the inter-conversion of D and L-glutamate enantiomers. Therefore, GluR is considered as an attractive target for the design of new antibacterial drugs. Here, we report the crystal structures of GluR from Streptococcus pyogenes in both inhibitor-free and inhibitor-bound forms. The inhibitor free GluR crystallized in two different forms, which diffracted to 2.25 A and 2.5 A resolution, while the inhibitor-bound crystal diffracted to 2.5 A resolution. GluR is composed of two domains of alpha/beta protein that are related by pseudo-2-fold symmetry and the active site is located at the domain interface. The inhibitor, gamma-2-naphthylmethyl-D-glutamate, which was reported earlier as a novel potent competitive inhibitor, makes several hydrogen bonds with protein atoms, and the naphthyl moiety is located in the hydrophobic pocket. The inhibitor binding induces a disorder in one of the loops near the active site. In both crystal forms, GluR exists as a dimer and the interactions seen at the dimer interface are almost identical. This agrees well with the results from gel filtration and dynamic light-scattering studies. | |||
Structural basis for glutamate racemase inhibition.,Kim KH, Bong YJ, Park JK, Shin KJ, Hwang KY, Kim EE J Mol Biol. 2007 Sep 14;372(2):434-43. Epub 2007 May 10. PMID:17658548<ref>PMID:17658548</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2oho" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Glutamate racemase 3D structures|Glutamate racemase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
[[Category: Streptococcus pyogenes M1 GAS]] | |||
[[Category: Kim EE]] | |||
== | |||
[[Category: | |||
[[Category: Streptococcus pyogenes]] | |||
[[Category: Kim | |||
Latest revision as of 11:57, 25 October 2023
Structural Basis for Glutamate Racemase InhibitorStructural Basis for Glutamate Racemase Inhibitor
Structural highlights
FunctionMURI_STRP1 Provides the (R)-glutamate required for cell wall biosynthesis (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedD-Glutamic acid is a required biosynthetic building block for peptidoglycan, and the enzyme glutamate racemase (GluR) catalyzes the inter-conversion of D and L-glutamate enantiomers. Therefore, GluR is considered as an attractive target for the design of new antibacterial drugs. Here, we report the crystal structures of GluR from Streptococcus pyogenes in both inhibitor-free and inhibitor-bound forms. The inhibitor free GluR crystallized in two different forms, which diffracted to 2.25 A and 2.5 A resolution, while the inhibitor-bound crystal diffracted to 2.5 A resolution. GluR is composed of two domains of alpha/beta protein that are related by pseudo-2-fold symmetry and the active site is located at the domain interface. The inhibitor, gamma-2-naphthylmethyl-D-glutamate, which was reported earlier as a novel potent competitive inhibitor, makes several hydrogen bonds with protein atoms, and the naphthyl moiety is located in the hydrophobic pocket. The inhibitor binding induces a disorder in one of the loops near the active site. In both crystal forms, GluR exists as a dimer and the interactions seen at the dimer interface are almost identical. This agrees well with the results from gel filtration and dynamic light-scattering studies. Structural basis for glutamate racemase inhibition.,Kim KH, Bong YJ, Park JK, Shin KJ, Hwang KY, Kim EE J Mol Biol. 2007 Sep 14;372(2):434-43. Epub 2007 May 10. PMID:17658548[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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