3mfv: Difference between revisions

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-{{STRUCTURE_3mfv|  PDB=3mfv  |  SCENE=  }}
-===Crystal structure of human arginase I in complex with 2-aminohomohistidine===
-{{ABSTRACT_PUBMED_20441173}}
-==Disease==
+==Crystal structure of human arginase I in complex with 2-aminohomohistidine==
-[[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>
+<StructureSection load='3mfv' size='340' side='right'caption='[[3mfv]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3mfv]] is a 2 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=3MFV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MFV 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=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=Z70:(2S)-2-AMINO-4-(2-AMINO-1H-IMIDAZOL-5-YL)BUTANOIC+ACID'>Z70</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=3mfv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mfv OCA], [https://pdbe.org/3mfv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mfv RCSB], [https://www.ebi.ac.uk/pdbsum/3mfv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mfv ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/ARGI1_HUMAN ARGI1_HUMAN] Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:[https://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>
+== Function ==
+[https://www.uniprot.org/uniprot/ARGI1_HUMAN ARGI1_HUMAN]
+== 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/mf/3mfv_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=3mfv ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Arginase, a key metalloenzyme of the urea cycle that converts L-arginine into L-ornithine and urea, is presently considered a pharmaceutical target for the management of diseases associated with aberrant l-arginine homeostasis, such as asthma, cardiovascular diseases, and erectile dysfunction. We now report the design, synthesis, and evaluation of a series of 2-aminoimidazole amino acid inhibitors in which the 2-aminoimidazole moiety serves as a guanidine mimetic. These compounds represent a new class of arginase inhibitors. The most potent inhibitor identified in this study, 2-(S)-amino-5-(2-aminoimidazol-1-yl)pentanoic acid (A1P, 10), binds to human arginase I with K(d) = 2 microM and significantly attenuates airways hyperresponsiveness in a murine model of allergic airways inflammation. These findings suggest that 2-aminoimidazole amino acids represent new leads for the development of arginase inhibitors with promising pharmacological profiles.
-==About this Structure==
+-aminoimidazole amino acids as inhibitors of the binuclear manganese metalloenzyme human arginase I.,Ilies M, Di Costanzo L, North ML, Scott JA, Christianson DW J Med Chem. 2010 May 27;53(10):4266-76. PMID:20441173<ref>PMID:20441173</ref>
-[[3mfv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MFV OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<ref group="xtra">PMID:020441173</ref><references group="xtra"/><references/>
+</div>
-[[Category: Arginase]]
+<div class="pdbe-citations 3mfv" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Arginase 3D structures|Arginase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Christianson, D W.]]
+[[Category: Large Structures]]
-[[Category: Costanzo, L Di.]]
+[[Category: Christianson DW]]
-[[Category: Hydrolase]]
+[[Category: Di Costanzo L]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Inhibition]]
-[[Category: Manganese coordination]]
-[[Category: Structure based design]]