4iu5: Difference between revisions
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== | ==Crystal structure of Leishmania mexicana arginase in complex with catalytic product L-ornithine== | ||
[[4iu5]] is a 1 chain structure with sequence from [ | <StructureSection load='4iu5' size='340' side='right'caption='[[4iu5]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
[[Category: | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4iu5]] is a 1 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=4IU5 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]] 1.95Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4iu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iu5 OCA], [https://pdbe.org/4iu5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iu5 RCSB], [https://www.ebi.ac.uk/pdbsum/4iu5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iu5 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q6TUJ5_LEIME Q6TUJ5_LEIME] | |||
<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> | |||
<div class="pdbe-citations 4iu5" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Arginase 3D structures|Arginase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Leishmania mexicana]] | [[Category: Leishmania mexicana]] | ||
[[Category: | [[Category: Christianson DW]] | ||
[[Category: | [[Category: D'Antonio EL]] | ||
[[Category: Dixit | [[Category: Gaur Dixit U]] | ||
[[Category: Hai | [[Category: Hai Y]] | ||
[[Category: Roberts | [[Category: Roberts SC]] | ||
[[Category: Ullman | [[Category: Ullman B]] | ||
[[Category: Wilson | [[Category: Wilson ME]] | ||
Latest revision as of 18:31, 20 September 2023
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
FunctionPublication 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. See AlsoReferences
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