1otx

Purine Nucleoside Phosphorylase M64V mutant

spinqualitylabelsall models 1otx, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1otx is a 3 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DEOD_ECOLI Cleavage of guanosine or inosine to respective bases and sugar-1-phosphate molecules.[HAMAP-Rule:MF_01627] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Activation of prodrugs by Escherichia coli purine nucleoside phosphorylase (PNP) provides a method for selectively killing tumor cells expressing a transfected PNP gene. This gene therapy approach requires matching a prodrug and a known enzymatic activity present only in tumor cells. The specificity of the method relies on avoiding prodrug cleavage by enzymes already present in the host cells or the intestinal flora. Using crystallographic and computer modeling methods as guides, we have redesigned E. coli PNP to cleave new prodrug substrates more efficiently than does the wild-type enzyme. In particular, the M64V PNP mutant cleaves 9-(6-deoxy-alpha-L-talofuranosyl)-6-methylpurine with a kcat/Km over 100 times greater than for native E. coli PNP. In a xenograft tumor experiment, this compound caused regression of tumors expressing the M64V PNP gene. Designer gene therapy using an Escherichia coli purine nucleoside phosphorylase/prodrug system.,Bennett EM, Anand R, Allan PW, Hassan AE, Hong JS, Levasseur DN, McPherson DT, Parker WB, Secrist JA 3rd, Sorscher EJ, Townes TM, Waud WR, Ealick SE Chem Biol. 2003 Dec;10(12):1173-81. PMID:14700625 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Purine nucleoside phosphorylase 3D structures

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