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==Crystal structure of Leishmania mexicana arginase in complex with catalytic product L-ornithine== | |||
<StructureSection load='4iu5' size='340' side='right' caption='[[4iu5]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4iu5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Leishmania_mexicana Leishmania mexicana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IU5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IU5 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ORN:L-ORNITHINE'>ORN</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ity|4ity]], [[4iu0|4iu0]], [[4iu1|4iu1]], [[4iu4|4iu4]], [[3gmz|3gmz]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ARG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5665 Leishmania mexicana])</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=4iu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iu5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iu5 RCSB], [http://www.ebi.ac.uk/pdbsum/4iu5 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Arginase from parasitic protozoa belonging to the genus Leishmania is a potential drug target for the treatment of leishmaniasis because this binuclear manganese metalloenzyme catalyzes the first committed step in the biosynthesis of polyamines that enable cell growth and survival. The high resolution X-ray crystal structures of the unliganded form of Leishmania mexicana arginase (LmARG) and four inhibitor complexes are now reported. These complexes include the reactive substrate analogue 2(S)-amino-6-boronohexanoic acid (ABH) and the hydroxylated substrate analogue nor-Nomega-hydroxy-L-arginine (nor-NOHA), which are the most potent arginase inhibitors known to date. Comparisons of the LmARG structure with that of the archetypal arginase, human arginase I, reveal that all residues important for substrate binding and catalysis are strictly conserved. However, three regions of tertiary structure differ between the parasitic enzyme and the human enzyme corresponding to the G62 - S71, L161 - C172, and I219 - V230 segments of LmARG. Additionally, variations are observed in salt link interactions that stabilize trimer assembly in LmARG. We also report biological studies in which we demonstrate that localization of LmARG to the glycosome, a unique subcellular organelle peculiar to Leishmania and related parasites, is essential for robust pathogenesis. | |||
Crystal structure of arginase from Leishmania mexicana and implications for the inhibition of polyamine biosynthesis in parasitic infections.,D'Antonio EL, Ullman B, Roberts SC, Dixit UG, Wilson ME, Hai Y, Christianson DW Arch Biochem Biophys. 2013 Apr 9. pii: S0003-9861(13)00103-3. doi:, 10.1016/j.abb.2013.03.015. PMID:23583962<ref>PMID:23583962</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Arginase]] | [[Category: Arginase]] | ||
[[Category: Leishmania mexicana]] | [[Category: Leishmania mexicana]] | ||
[[Category: Antonio, E L.D | [[Category: Antonio, E L.D]] | ||
[[Category: Christianson, D W | [[Category: Christianson, D W]] | ||
[[Category: Dixit, U Gaur | [[Category: Dixit, U Gaur]] | ||
[[Category: Hai, Y | [[Category: Hai, Y]] | ||
[[Category: Roberts, S C | [[Category: Roberts, S C]] | ||
[[Category: Ullman, B | [[Category: Ullman, B]] | ||
[[Category: Wilson, M E | [[Category: Wilson, M E]] | ||
[[Category: Arginase fold]] | [[Category: Arginase fold]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
Revision as of 15:26, 5 January 2015
Crystal structure of Leishmania mexicana arginase in complex with catalytic product L-ornithineCrystal structure of Leishmania mexicana arginase in complex with catalytic product L-ornithine
Structural highlights
Publication Abstract from PubMedArginase from parasitic protozoa belonging to the genus Leishmania is a potential drug target for the treatment of leishmaniasis because this binuclear manganese metalloenzyme catalyzes the first committed step in the biosynthesis of polyamines that enable cell growth and survival. The high resolution X-ray crystal structures of the unliganded form of Leishmania mexicana arginase (LmARG) and four inhibitor complexes are now reported. These complexes include the reactive substrate analogue 2(S)-amino-6-boronohexanoic acid (ABH) and the hydroxylated substrate analogue nor-Nomega-hydroxy-L-arginine (nor-NOHA), which are the most potent arginase inhibitors known to date. Comparisons of the LmARG structure with that of the archetypal arginase, human arginase I, reveal that all residues important for substrate binding and catalysis are strictly conserved. However, three regions of tertiary structure differ between the parasitic enzyme and the human enzyme corresponding to the G62 - S71, L161 - C172, and I219 - V230 segments of LmARG. Additionally, variations are observed in salt link interactions that stabilize trimer assembly in LmARG. We also report biological studies in which we demonstrate that localization of LmARG to the glycosome, a unique subcellular organelle peculiar to Leishmania and related parasites, is essential for robust pathogenesis. Crystal structure of arginase from Leishmania mexicana and implications for the inhibition of polyamine biosynthesis in parasitic infections.,D'Antonio EL, Ullman B, Roberts SC, Dixit UG, Wilson ME, Hai Y, Christianson DW Arch Biochem Biophys. 2013 Apr 9. pii: S0003-9861(13)00103-3. doi:, 10.1016/j.abb.2013.03.015. PMID:23583962[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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