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| | ==Crystal structure of Leishmania mexicana arginase in complex with inhibitor BEC== | | ==Crystal structure of Leishmania mexicana arginase in complex with inhibitor BEC== |
| - | <StructureSection load='4iu4' size='340' side='right' caption='[[4iu4]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='4iu4' size='340' side='right'caption='[[4iu4]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4iu4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Leime Leime]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IU4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IU4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4iu4]] 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=4IU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IU4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=S2C:S-2-(BORONOETHYL)-L-CYSTEINE'>S2C</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=S2C:S-2-(BORONOETHYL)-L-CYSTEINE'>S2C</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3gmz|3gmz]], [[4iu0|4iu0]], [[4iu1|4iu1]], [[1wva|1wva]], [[4iu5|4iu5]]</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=4iu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iu4 OCA], [https://pdbe.org/4iu4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iu4 RCSB], [https://www.ebi.ac.uk/pdbsum/4iu4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iu4 ProSAT]</span></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 LEIME])</td></tr>
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| - | <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>
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| - | <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=4iu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iu4 OCA], [http://pdbe.org/4iu4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iu4 RCSB], [http://www.ebi.ac.uk/pdbsum/4iu4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iu4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q6TUJ5_LEIME Q6TUJ5_LEIME] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Arginase|Arginase]] | + | *[[Arginase 3D structures|Arginase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arginase]] | + | [[Category: Large Structures]] |
| - | [[Category: Leime]] | + | [[Category: Leishmania mexicana]] |
| - | [[Category: Antonio, E L.D]] | + | [[Category: Christianson DW]] |
| - | [[Category: Christianson, D W]] | + | [[Category: D'Antonio EL]] |
| - | [[Category: Dixit, U Gaur]] | + | [[Category: Gaur Dixit U]] |
| - | [[Category: Hai, Y]] | + | [[Category: Hai Y]] |
| - | [[Category: Roberts, S C]] | + | [[Category: Roberts SC]] |
| - | [[Category: Ullman, B]] | + | [[Category: Ullman B]] |
| - | [[Category: Wilson, M E]] | + | [[Category: Wilson ME]] |
| - | [[Category: Arginase fold]]
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| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
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| Structural highlights
Function
Q6TUJ5_LEIME
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ D'Antonio EL, Ullman B, Roberts SC, Dixit UG, Wilson ME, Hai Y, Christianson DW. Crystal structure of arginase from Leishmania mexicana and implications for the inhibition of polyamine biosynthesis in parasitic infections. Arch Biochem Biophys. 2013 Apr 9. pii: S0003-9861(13)00103-3. doi:, 10.1016/j.abb.2013.03.015. PMID:23583962 doi:10.1016/j.abb.2013.03.015
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