4ie2: Difference between revisions
New page: '''Unreleased structure''' The entry 4ie2 is ON HOLD Authors: Cousido-Siah, A., Mitschler, A., Ruiz, F.X., Beckett ,P., Van Zandt, M.C., Ji,M.K., Whitehouse, D., Ryder, T., Jagdmann, E.... |
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==Crystal structure of human Arginase-2 complexed with inhibitor 1h== | |||
<StructureSection load='4ie2' size='340' side='right'caption='[[4ie2]], [[Resolution|resolution]] 2.21Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ie2]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IE2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IE2 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]] 2.2082Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1EC:[(5R)-5-AMINO-5-CARBOXY-8-HYDROXYOCTYL](TRIHYDROXY)BORATE(1-)'>1EC</scene>, <scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=4ie2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ie2 OCA], [https://pdbe.org/4ie2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ie2 RCSB], [https://www.ebi.ac.uk/pdbsum/4ie2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ie2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ARGI2_HUMAN ARGI2_HUMAN] May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis. Extrahepatic arginase functions to regulate L-arginine bioavailability to NO synthase. Since NO synthase is found in the penile corpus cavernosum smooth muscle, the clitoral corpus cavernosum and the vagina, arginase II plays a role in both male and female sexual arousal. It is therefore a potential target for the treatment of male and female sexual arousal disorders. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Substitution at the alpha center of the known human arginase inhibitor 2-amino-6-boronohexanoic acid (ABH) is acceptable in the active site pockets of both human arginase I and arginase II. In particular, substituents with a tertiary amine linked via a two carbon chain show improved inhibitory potency for both enzyme isoforms. This potency improvement can be rationalized by X-ray crystallography, which shows a water-mediated contact between the basic nitrogen and the carboxylic acid side chain of Asp200, which is situated at the mouth of the active site pocket of arginase II (Asp181 in arginase I). We believe that this is the first literature report of compounds with improved arginase inhibitory activity, relative to ABH, and represents a promising starting point for further optimization of in vitro potency and the identification of better tool molecules for in vivo investigations of the potential pathophysiological roles of arginases. | |||
2-Substituted-2-amino-6-boronohexanoic acids as arginase inhibitors.,Golebiowski A, Paul Beckett R, Van Zandt M, Ji MK, Whitehouse D, Ryder TR, Jagdmann E, Andreoli M, Mazur A, Padmanilayam M, Cousido-Siah A, Mitschler A, Ruiz FX, Podjarny A, Schroeter H Bioorg Med Chem Lett. 2013 Apr 1;23(7):2027-30. doi: 10.1016/j.bmcl.2013.02.024. , Epub 2013 Feb 13. PMID:23453840<ref>PMID:23453840</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4ie2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Arginase 3D structures|Arginase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Andreoli M]] | |||
[[Category: Beckett P]] | |||
[[Category: Cousido-Siah A]] | |||
[[Category: Golebiowski A]] | |||
[[Category: Jagdmann E]] | |||
[[Category: Ji MK]] | |||
[[Category: Mazur A]] | |||
[[Category: Mitschler A]] | |||
[[Category: Padmanilayam M]] | |||
[[Category: Podjarny A]] | |||
[[Category: Ruiz FX]] | |||
[[Category: Ryder T]] | |||
[[Category: Schroeter H]] | |||
[[Category: Van Zandt MC]] | |||
[[Category: Whitehouse D]] | |||
Latest revision as of 18:21, 20 September 2023
Crystal structure of human Arginase-2 complexed with inhibitor 1hCrystal structure of human Arginase-2 complexed with inhibitor 1h
Structural highlights
FunctionARGI2_HUMAN May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis. Extrahepatic arginase functions to regulate L-arginine bioavailability to NO synthase. Since NO synthase is found in the penile corpus cavernosum smooth muscle, the clitoral corpus cavernosum and the vagina, arginase II plays a role in both male and female sexual arousal. It is therefore a potential target for the treatment of male and female sexual arousal disorders. Publication Abstract from PubMedSubstitution at the alpha center of the known human arginase inhibitor 2-amino-6-boronohexanoic acid (ABH) is acceptable in the active site pockets of both human arginase I and arginase II. In particular, substituents with a tertiary amine linked via a two carbon chain show improved inhibitory potency for both enzyme isoforms. This potency improvement can be rationalized by X-ray crystallography, which shows a water-mediated contact between the basic nitrogen and the carboxylic acid side chain of Asp200, which is situated at the mouth of the active site pocket of arginase II (Asp181 in arginase I). We believe that this is the first literature report of compounds with improved arginase inhibitory activity, relative to ABH, and represents a promising starting point for further optimization of in vitro potency and the identification of better tool molecules for in vivo investigations of the potential pathophysiological roles of arginases. 2-Substituted-2-amino-6-boronohexanoic acids as arginase inhibitors.,Golebiowski A, Paul Beckett R, Van Zandt M, Ji MK, Whitehouse D, Ryder TR, Jagdmann E, Andreoli M, Mazur A, Padmanilayam M, Cousido-Siah A, Mitschler A, Ruiz FX, Podjarny A, Schroeter H Bioorg Med Chem Lett. 2013 Apr 1;23(7):2027-30. doi: 10.1016/j.bmcl.2013.02.024. , Epub 2013 Feb 13. PMID:23453840[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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