View source for 3kv2

==HIGH RESOLUTION STRUCTURE OF HUMAN ARGINASE I IN COMPLEX WITH THE STRONG INHIBITOR N(omega)-hydroxy-nor-L-arginine (nor-NOHA)==
<StructureSection load='3kv2' size='340' side='right' caption='[[3kv2]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3kv2]] 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=3KV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KV2 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NNH:NOR-N-OMEGA-HYDROXY-L-ARGININE'>NNH</scene></td></tr>
<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>
<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>
<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=3kv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kv2 OCA], [http://pdbe.org/3kv2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kv2 RCSB], [http://www.ebi.ac.uk/pdbsum/3kv2 PDBsum]</span></td></tr>
</table>
== 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>  
== 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/kv/3kv2_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=3kv2 ConSurf].
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== Publication Abstract from PubMed ==
Human arginase I is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of L-arginine to generate L-ornithine and urea. We demonstrate that N-hydroxy-L-arginine (NOHA) binds to this enzyme with K(d)=3.6 microM, and nor-N-hydroxy-L-arginine (nor-NOHA) binds with K(d)=517 nM (surface plasmon resonance) or K(d) approximately 50 nM (isothermal titration calorimetry). Crystals of human arginase I complexed with NOHA and nor-NOHA afford 2.04 and 1.55 A resolution structures, respectively, which are significantly improved in comparison with previously-determined structures of the corresponding complexes with rat arginase I. Higher resolution structures clarify the binding interactions of the inhibitors. Finally, the crystal structure of the complex with L-lysine (K(d)=13 microM) is reported at 1.90 A resolution. This structure confirms the importance of hydrogen bond interactions with inhibitor alpha-carboxylate and alpha-amino groups as key specificity determinants of amino acid recognition in the arginase active site.

Inhibition of human arginase I by substrate and product analogues.,Di Costanzo L, Ilies M, Thorn KJ, Christianson DW Arch Biochem Biophys. 2010 Apr 15;496(2):101-8. Epub 2010 Feb 12. PMID:20153713<ref>PMID:20153713</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3kv2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Arginase|Arginase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Arginase]]
[[Category: Human]]
[[Category: Christianson, D W]]
[[Category: Costanzo, L Di]]
[[Category: Arginine metabolism]]
[[Category: Disease mutation]]
[[Category: High resolution]]
[[Category: Hydrolase]]
[[Category: Manganese]]
[[Category: Metal-binding]]
[[Category: Nor-noha]]
[[Category: Phosphoprotein]]
[[Category: Strong inhibitor]]
[[Category: Urea cycle]]