3e9b: Difference between revisions
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< | ==X-ray structure of rat arginase I-T135A mutant: the complex with BEC== | ||
<StructureSection load='3e9b' size='340' side='right'caption='[[3e9b]], [[Resolution|resolution]] 2.15Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3e9b]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E9B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E9B 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]] 2.15Å</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=S2C:S-2-(BORONOETHYL)-L-CYSTEINE'>S2C</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=3e9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e9b OCA], [https://pdbe.org/3e9b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e9b RCSB], [https://www.ebi.ac.uk/pdbsum/3e9b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e9b ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ARGI1_RAT ARGI1_RAT] | |||
== 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/e9/3e9b_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=3e9b ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Arginase is a binuclear manganese metalloenzyme that serves as a therapeutic target for the treatment of asthma, erectile dysfunction, and atherosclerosis. In order to better understand the molecular basis of inhibitor affinity, we have employed site-directed mutagenesis, enzyme kinetics, and X-ray crystallography to probe the molecular recognition of the amino acid moiety (i.e., the alpha-amino and alpha-carboxylate groups) of substrate l-arginine and inhibitors in the active site of arginase I. Specifically, we focus on (1) a water-mediated hydrogen bond between the substrate alpha-carboxylate and T135, (2) a direct hydrogen bond between the substrate alpha-carboxylate and N130, and (3) a direct charged hydrogen bond between the substrate alpha-amino group and D183. Amino acid substitutions for T135, N130, and D183 generally compromise substrate affinity as reflected by increased K(M) values but have less pronounced effects on catalytic function as reflected by minimal variations of k(cat). As with substrate K(M) values, inhibitor K(d) values increase for binding to enzyme mutants and suggest that the relative contribution of intermolecular interactions to amino acid affinity in the arginase active site is water-mediated hydrogen bond < direct hydrogen bond < direct charged hydrogen bond. Structural comparisons of arginase with the related binuclear manganese metalloenzymes agmatinase and proclavaminic acid amidinohydrolase suggest that the evolution of substrate recognition in the arginase fold occurs by mutation of residues contained in specificity loops flanking the mouth of the active site (especially loops 4 and 5), thereby allowing diverse guanidinium substrates to be accommodated for catalysis. | |||
Probing the specificity determinants of amino acid recognition by arginase.,Shishova EY, Di Costanzo L, Emig FA, Ash DE, Christianson DW Biochemistry. 2009 Jan 13;48(1):121-31. PMID:19093830<ref>PMID:19093830</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3e9b" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Arginase 3D structures|Arginase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
== | |||
< | |||
[[Category: | |||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Christianson | [[Category: Christianson DW]] | ||
[[Category: Costanzo | [[Category: Di Costanzo L]] | ||
[[Category: Shishova | [[Category: Shishova EY]] | ||
Latest revision as of 15:59, 30 August 2023
X-ray structure of rat arginase I-T135A mutant: the complex with BECX-ray structure of rat arginase I-T135A mutant: the complex with BEC
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedArginase is a binuclear manganese metalloenzyme that serves as a therapeutic target for the treatment of asthma, erectile dysfunction, and atherosclerosis. In order to better understand the molecular basis of inhibitor affinity, we have employed site-directed mutagenesis, enzyme kinetics, and X-ray crystallography to probe the molecular recognition of the amino acid moiety (i.e., the alpha-amino and alpha-carboxylate groups) of substrate l-arginine and inhibitors in the active site of arginase I. Specifically, we focus on (1) a water-mediated hydrogen bond between the substrate alpha-carboxylate and T135, (2) a direct hydrogen bond between the substrate alpha-carboxylate and N130, and (3) a direct charged hydrogen bond between the substrate alpha-amino group and D183. Amino acid substitutions for T135, N130, and D183 generally compromise substrate affinity as reflected by increased K(M) values but have less pronounced effects on catalytic function as reflected by minimal variations of k(cat). As with substrate K(M) values, inhibitor K(d) values increase for binding to enzyme mutants and suggest that the relative contribution of intermolecular interactions to amino acid affinity in the arginase active site is water-mediated hydrogen bond < direct hydrogen bond < direct charged hydrogen bond. Structural comparisons of arginase with the related binuclear manganese metalloenzymes agmatinase and proclavaminic acid amidinohydrolase suggest that the evolution of substrate recognition in the arginase fold occurs by mutation of residues contained in specificity loops flanking the mouth of the active site (especially loops 4 and 5), thereby allowing diverse guanidinium substrates to be accommodated for catalysis. Probing the specificity determinants of amino acid recognition by arginase.,Shishova EY, Di Costanzo L, Emig FA, Ash DE, Christianson DW Biochemistry. 2009 Jan 13;48(1):121-31. PMID:19093830[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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