3sl0: Difference between revisions
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==Crystal Structure of P. falciparum arginase complexed with 2-amino-6-borono-2-(difluoromethyl)hexanoic acid== | ==Crystal Structure of P. falciparum arginase complexed with 2-amino-6-borono-2-(difluoromethyl)hexanoic acid== | ||
<StructureSection load='3sl0' size='340' side='right' caption='[[3sl0]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='3sl0' size='340' side='right' caption='[[3sl0]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3sl0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3sl0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SL0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SL0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FB5:2-(DIFLUOROMETHYL)-6-(DIHYDROXYBORANYL)-L-NORLEUCINE'>FB5</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FB5:2-(DIFLUOROMETHYL)-6-(DIHYDROXYBORANYL)-L-NORLEUCINE'>FB5</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mmr|3mmr]], [[3sl1|3sl1]], [[3sjt|3sjt]], [[3skk|3skk]], [[3gmz|3gmz]], [[3gn0|3gn0]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mmr|3mmr]], [[3sl1|3sl1]], [[3sjt|3sjt]], [[3skk|3skk]], [[3gmz|3gmz]], [[3gn0|3gn0]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PFI0320w ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PFI0320w ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</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='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=3sl0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sl0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sl0 RCSB], [http://www.ebi.ac.uk/pdbsum/3sl0 PDBsum]</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=3sl0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sl0 OCA], [http://pdbe.org/3sl0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sl0 RCSB], [http://www.ebi.ac.uk/pdbsum/3sl0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sl0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3sl0" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Arginase]] | [[Category: Arginase]] | ||
[[Category: | [[Category: Plaf7]] | ||
[[Category: Christianson, D W]] | [[Category: Christianson, D W]] | ||
[[Category: Dowling, D P]] | [[Category: Dowling, D P]] | ||
Revision as of 22:47, 11 August 2016
Crystal Structure of P. falciparum arginase complexed with 2-amino-6-borono-2-(difluoromethyl)hexanoic acidCrystal Structure of P. falciparum arginase complexed with 2-amino-6-borono-2-(difluoromethyl)hexanoic acid
Structural highlights
Publication Abstract from PubMedArginase is a binuclear manganese metalloenzyme that hydrolyzes l-arginine to form l-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. Accordingly, arginase inhibitors may be therapeutically useful. Continuing our efforts to expand the chemical space of arginase inhibitor design and inspired by the binding of 2-(difluoromethyl)-l-ornithine to human arginase I, we now report the first study of the binding of alpha,alpha-disubstituted amino acids to arginase. Specifically, we report the design, synthesis, and assay of racemic 2-amino-6-borono-2-methylhexanoic acid and racemic 2-amino-6-borono-2-(difluoromethyl)hexanoic acid. X-ray crystal structures of human arginase I and Plasmodium falciparum arginase complexed with these inhibitors reveal the exclusive binding of the l-stereoisomer; the additional alpha-substituent of each inhibitor is readily accommodated and makes new intermolecular interactions in the outer active site of each enzyme. Therefore, this work highlights a new region of the protein surface that can be targeted for additional affinity interactions, as well as the first comparative structural insights on inhibitor discrimination between a human and a parasitic arginase. Binding of alpha,alpha-Disubstituted Amino Acids to Arginase Suggests New Avenues for Inhibitor Design.,Ilies M, Di Costanzo L, Dowling DP, Thorn KJ, Christianson DW J Med Chem. 2011 Jul 18. PMID:21728378[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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