4ie1

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{{STRUCTURE_4ie1| PDB=4ie1 | SCENE= }}
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==Crystal structure of human Arginase-1 complexed with inhibitor 1h==
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===Crystal structure of human Arginase-1 complexed with inhibitor 1h===
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<StructureSection load='4ie1' size='340' side='right' caption='[[4ie1]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23453840}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4ie1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IE1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IE1 FirstGlance]. <br>
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==Disease==
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1EC:[(5R)-5-AMINO-5-CARBOXY-8-HYDROXYOCTYL](TRIHYDROXY)BORATE(1-)'>1EC</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1d3v|1d3v]], [[2aeb|2aeb]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ARG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Arginase Arginase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.1 3.5.3.1] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ie1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ie1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ie1 RCSB], [http://www.ebi.ac.uk/pdbsum/4ie1 PDBsum]</span></td></tr>
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</table>
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== Disease ==
[[http://www.uniprot.org/uniprot/ARGI1_HUMAN ARGI1_HUMAN]] Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:[http://omim.org/entry/207800 207800]]; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia.<ref>PMID:1463019</ref> <ref>PMID:7649538</ref>
[[http://www.uniprot.org/uniprot/ARGI1_HUMAN ARGI1_HUMAN]] Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:[http://omim.org/entry/207800 207800]]; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia.<ref>PMID:1463019</ref> <ref>PMID:7649538</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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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>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4ie1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IE1 OCA].
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</div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:023453840</ref><references group="xtra"/><references/>
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*[[Arginase|Arginase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Arginase]]
[[Category: Arginase]]
[[Category: Human]]
[[Category: Human]]
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[[Category: Andreoli, M.]]
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[[Category: Andreoli, M]]
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[[Category: Beckett, P.]]
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[[Category: Beckett, P]]
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[[Category: Cousido-Siah, A.]]
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[[Category: Cousido-Siah, A]]
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[[Category: Golebiowski, A.]]
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[[Category: Golebiowski, A]]
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[[Category: Jagdmann, E.]]
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[[Category: Jagdmann, E]]
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[[Category: Ji, M K.]]
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[[Category: Ji, M K]]
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[[Category: Mazur, A.]]
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[[Category: Mazur, A]]
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[[Category: Mitschler, A.]]
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[[Category: Mitschler, A]]
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[[Category: Padmanilayam, M.]]
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[[Category: Padmanilayam, M]]
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[[Category: Podjarny, A.]]
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[[Category: Podjarny, A]]
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[[Category: Ruiz, F X.]]
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[[Category: Ruiz, F X]]
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[[Category: Ryder, T.]]
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[[Category: Ryder, T]]
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[[Category: Schroeter, H.]]
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[[Category: Schroeter, H]]
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[[Category: Whitehouse, D.]]
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[[Category: Whitehouse, D]]
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[[Category: Zandt, M C.Van.]]
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[[Category: Zandt, M C.Van]]
[[Category: Alpha/beta fold]]
[[Category: Alpha/beta fold]]
[[Category: Arginine metabolism]]
[[Category: Arginine metabolism]]

Revision as of 18:41, 24 December 2014

Crystal structure of human Arginase-1 complexed with inhibitor 1h

4ie1, resolution 2.00Å

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