4EAR
Crystal structure of purine nucleoside phosphorylase (W16Y, W94Y, W178Y, H257W) mutant from human complexed with DADMe-ImmG and phosphate
Summary for 4EAR
| Entry DOI | 10.2210/pdb4ear/pdb |
| Descriptor | Purine nucleoside phosphorylase, 2-amino-7-{[(3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidin-1-yl]methyl}-3,5-dihydro-4H-pyrrolo[3,2-d]pyrimidin-4-one, PHOSPHATE ION, ... (4 entities in total) |
| Functional Keywords | pnp, immucillin, purine nucleoside phosphorylase, nucleoside binding, purine base binding, purine-nucleoside phosphorylase activity, drug binding, transferase activity, transferring glycosyl groups, phosphate ion binding, cytosol, 6-fluoro-l-tryptophan, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm, cytoskeleton (By similarity): P00491 |
| Total number of polymer chains | 3 |
| Total formula weight | 109558.15 |
| Authors | Haapalainen, A.M.,Ho, M.C.,Suarez, J.J.,Almo, S.C.,Schramm, V.L. (deposition date: 2012-03-22, release date: 2013-02-06, Last modification date: 2024-10-30) |
| Primary citation | Suarez, J.,Haapalainen, A.M.,Cahill, S.M.,Ho, M.C.,Yan, F.,Almo, S.C.,Schramm, V.L. Catalytic Site Conformations in Human PNP by (19)F-NMR and Crystallography. Chem.Biol., 20:212-222, 2013 Cited by PubMed Abstract: Purine nucleoside phosphorylase (PNP) is a target for leukemia, gout, and autoimmune disorders. Dynamic motion of catalytic site loops has been implicated in catalysis, but experimental evidence was lacking. We replaced catalytic site groups His257 or His64 with 6-fluoro-tryptophan (6FW) as site-specific NMR probes. Conformational adjustments in the 6FW-His257-helical and His64-6FW-loop regions were characterized in PNP phosphate-bound enzyme and in complexes with catalytic site ligands, including transition state analogs. Chemical shift and line-shape changes associated with these complexes revealed dynamic coexistence of several conformational states in these regions in phosphate-bound enzyme and altered or single conformations in other complexes. These conformations were also characterized by X-ray crystallography. Specific (19)F-Trp labels and X-ray crystallography provide multidimensional characterization of conformational states for free, catalytic, and inhibited complexes of human PNP. PubMed: 23438750DOI: 10.1016/j.chembiol.2013.01.009 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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