3mb8

Crystal structure of purine nucleoside phosphorylase from toxoplasma gondii in complex with immucillin-H

spinqualitylabelsall models 3mb8, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3mb8 is a 2 chain structure with sequence from Toxoplasma gondii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: GOL, IMH, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q2HXR2_TOXGO Publication Abstract from PubMed The intracellular pathogen Toxoplasma gondii is a purine auxotroph that relies on purine salvage for proliferation. We have optimized T. gondii purine nucleoside phosphorylase (TgPNP) stability and crystallized TgPNP with phosphate and Immucillin-H, a transition-state analogue that has high affinity for the enzyme. Immucillin-H bound to TgPNP with a dissociation constant of 370 pM, the highest affinity of eleven immucillins selected to probe the catalytic site. The specificity for transition-state analogues indicated an early dissociative transition state for TgPNP. Compared with PfPNP, large substituents surrounding the 5' -hydroxyl group of inhibitors demonstrate reduced capacity for TgPNP inhibition. Catalytic discrimination against large 5' groups is consistent with the inability of TgPNP to catalyze the phosphorylysis of 5' -methylthioinosine to hypoxanthine. In contrast to mammalian PNP, the 2' -hydroxyl group is crucial for inhibitor binding in the catalytic site of TgPNP. This first crystal structure of TgPNP describes the basis for discrimination against 5' -methylthioinosine and similarly 5' -hydroxy-substituted immucillins; structural differences reflect the unique adaptations of purine salvage pathways of Apicomplexa. INHIBITION AND STRUCTURE OF TOXOPLASMA GONDII PURINE NUCLEOSIDE PHOSPHORYLASE.,Donaldson TM, Cassera MB, Ho MC, Zhan C, Merino EF, Evans GB, Tyler PC, Almo SC, Schramm VL, Kim K Eukaryot Cell. 2014 Feb 28. PMID:24585883 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Purine nucleoside phosphorylase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA