4iu5

Crystal structure of Leishmania mexicana arginase in complex with catalytic product L-ornithine

spinqualitylabelsall models 4iu5, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4iu5 is a 1 chain structure with sequence from Leishmania mexicana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: GOL, MN, ORN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Arginase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA