4q42: Difference between revisions
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New page: '''Unreleased structure''' The entry 4q42 is ON HOLD Authors: Hai, Y., Edwards, J.E., Van Zandt, M.C., Hoffmann, K.F., Christianson, D.W. Description: Crystal structure of Schistosoma ... |
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The | ==Crystal structure of Schistosoma mansoni arginase in complex with L-ornithine== | ||
<StructureSection load='4q42' size='340' side='right'caption='[[4q42]], [[Resolution|resolution]] 2.05Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4q42]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q42 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Q42 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]] 2.051Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ORN:L-ORNITHINE'>ORN</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=4q42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q42 OCA], [https://pdbe.org/4q42 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4q42 RCSB], [https://www.ebi.ac.uk/pdbsum/4q42 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4q42 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q6WVP6_SCHMA Q6WVP6_SCHMA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The X-ray crystal structure of arginase from Schistosoma mansoni (SmARG) and the structures of its complexes with several amino acid inhibitors have been determined at atomic resolution. SmARG is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of l-arginine to form l-ornithine and urea, and this enzyme is upregulated in all forms of the parasite that interact with the human host. Current hypotheses suggest that parasitic arginases could play a role in host immune evasion by depleting pools of substrate l-arginine that would otherwise be utilized for NO biosynthesis and NO-dependent processes in the immune response. Although the amino acid sequence of SmARG is only 42% identical with that of human arginase I, residues important for substrate binding and catalysis are strictly conserved. In general, classical amino acid inhibitors such as 2(S)-amino-6-boronohexanoic acid (ABH) tend to bind more weakly to SmARG than to human arginase I despite identical inhibitor binding modes in each enzyme active site. The identification of a patch on the enzyme surface capable of accommodating the additional Calpha substitutent of an alpha,alpha-disubstituted amino acid inhibitor suggests that such inhibitors could exhibit higher affinity and biological activity. The structures of SmARG complexed with two different alpha,alpha-disubstituted derivatives of ABH are presented and provide a proof of concept for this approach in the enhancement of enzyme-inhibitor affinity. | |||
Crystal Structure of Schistosoma mansoni Arginase, a Potential Drug Target for the Treatment of Schistosomiasis.,Hai Y, Edwards JE, Van Zandt MC, Hoffmann KF, Christianson DW Biochemistry. 2014 Jul 22;53(28):4671-84. doi: 10.1021/bi5004519. Epub 2014 Jul, 9. PMID:25007099<ref>PMID:25007099</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4q42" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Arginase 3D structures|Arginase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Schistosoma mansoni]] | |||
[[Category: Christianson DW]] | |||
[[Category: Edwards JE]] | |||
[[Category: Hai Y]] | |||
[[Category: Hoffmann KF]] | |||
[[Category: Van Zandt MC]] | |||
