4EB8

Crystal structure of purine nucleoside phosphorylase (W16Y, W94Y, W178Y, H257W) mutant from human complexed with DADMe-ImmG and phosphate

4EB8 の概要

• エントリーDOI: 10.2210/pdb4eb8/pdb
• 関連するPDBエントリー: 4EAR
• 分子名称: Purine nucleoside phosphorylase, PHOSPHATE ION, 2-amino-7-{[(3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidin-1-yl]methyl}-3,5-dihydro-4H-pyrrolo[3,2-d]pyrimidin-4-one, ... (5 entities in total)
• 機能のキーワード: pnp, immucillin, purine nucleoside phosphorylase, nucleoside binding, purine base binding, purine-nucleoside phosphorylase activity, drug binding, transferase activity, transferring glycosyl groups, phosphate ion binding, intracellular, cytosol, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytoskeleton (By similarity): P00491
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 109628.32

構造登録者

Ho, M.C.,Haapalainen, A.M.,Suarez, J.J.,Almo, S.C.,Schramm, V.L. (登録日: 2012-03-23, 公開日: 2013-02-06, 最終更新日: 2024-02-28)

主引用文献

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

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: 23438750
DOI: 10.1016/j.chembiol.2013.01.009

実験手法

X-RAY DIFFRACTION (2.3 Å)