View source for 4ixu


==Crystal structure of human Arginase-2 complexed with inhibitor 11d: {(5R)-5-amino-5-carboxy-5-[(3-endo)-8-(3,4-dichlorobenzyl)-8-azabicyclo[3.2.1]oct-3-yl]pentyl}(trihydroxy)borate(1-)==
<StructureSection load='4ixu' size='340' side='right'caption='[[4ixu]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ixu]] 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=4IXU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IXU 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=38I:{(5R)-5-AMINO-5-CARBOXY-5-[(3-ENDO)-8-(3,4-DICHLOROBENZYL)-8-AZABICYCLO[3.2.1]OCT-3-YL]PENTYL}(TRIHYDROXY)BORATE(1-)'>38I</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=4ixu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ixu OCA], [https://pdbe.org/4ixu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ixu RCSB], [https://www.ebi.ac.uk/pdbsum/4ixu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ixu 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 ==
The Ugi reaction has been successfully applied to the synthesis of novel arginase inhibitors. In an effort to decrease conformational flexibility of the previously reported series of 2-amino-6-boronohexanoic acid (ABH) analogs 1, we designed and synthesized a series of compounds, 2, in which a piperidine ring is linked directly to a quaternary amino acid center. Further improvement of in vitro activity was achieved by adding two carbon bridge in the piperidine ring, that is, tropane analogs 11. These improvements in activity are rationalized by X-ray crystallography analysis, which show that the tropane ring nitrogen atom moves into direct contact with Asp202 (arginase II numbering). The synthetic routes described here enabled the design of novel arginase inhibitors with improved potency and markedly different physico-chemical properties compared to ABH. Compound 11c represents the most in vitro active arginase inhibitor reported to date.

Synthesis of quaternary alpha-amino acid-based arginase inhibitors via the Ugi reaction.,Golebiowski A, Whitehouse D, Beckett RP, Van Zandt M, Ji MK, Ryder TR, Jagdmann E, Andreoli M, Lee Y, Sheeler R, Conway B, Olczak J, Mazur M, Czestkowski W, Piotrowska W, Cousido-Siah A, Ruiz FX, Mitschler A, Podjarny A, Schroeter H Bioorg Med Chem Lett. 2013 Sep 1;23(17):4837-41. doi: 10.1016/j.bmcl.2013.06.092., Epub 2013 Jul 8. PMID:23886684<ref>PMID:23886684</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ixu" 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: Czestkowski W]]
[[Category: Golebiowski A]]
[[Category: Jagdmann R]]
[[Category: Ji MK]]
[[Category: Mazur M]]
[[Category: Mitschler A]]
[[Category: Olczak J]]
[[Category: Piotrowska W]]
[[Category: Podjarny A]]
[[Category: Ruiz FX]]
[[Category: Ryder T]]
[[Category: Schroeter H]]
[[Category: Van Zandt MC]]
[[Category: Whitehouse D]]