1ou4

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{{STRUCTURE_1ou4| PDB=1ou4 | SCENE= }}
{{STRUCTURE_1ou4| PDB=1ou4 | SCENE= }}
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'''Native PNP +Talo'''
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===Native PNP +Talo===
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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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(as it appears on PubMed at http://www.pubmed.gov), where 14700625 is the PubMed ID number.
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{{ABSTRACT_PUBMED_14700625}}
==About this Structure==
==About this Structure==
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[[Category: Native]]
[[Category: Native]]
[[Category: Talo]]
[[Category: Talo]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:54:00 2008''

Revision as of 17:54, 28 July 2008

Image:1ou4.png

Template:STRUCTURE 1ou4

Native PNP +Talo

Template:ABSTRACT PUBMED 14700625

About this Structure

1OU4 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

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

Page seeded by OCA on Mon Jul 28 20:54:00 2008

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