1otx: Difference between revisions

Revision as of 08:22, 29 July 2008

This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.

File:1otx.png

Template:STRUCTURE 1otx

Purine Nucleoside Phosphorylase M64V mutantPurine Nucleoside Phosphorylase M64V mutant

Template:ABSTRACT PUBMED 14700625

About this StructureAbout this Structure

1OTX is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

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

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OCA

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-'''Purine Nucleoside Phosphorylase M64V mutant'''
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-==Overview==
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-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.
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