1ou4: Difference between revisions

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[[Image:1ou4.jpg|left|200px]]
{{Seed}}
[[Image:1ou4.png|left|200px]]


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{{STRUCTURE_1ou4|  PDB=1ou4  |  SCENE=  }}  
{{STRUCTURE_1ou4|  PDB=1ou4  |  SCENE=  }}  


'''Native PNP +Talo'''
===Native PNP +Talo===




==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.
The line below this paragraph, {{ABSTRACT_PUBMED_14700625}}, adds the Publication Abstract to the page
(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]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 04:16:55 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:54:00 2008''
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