View source for 1otx

[[Image:1otx.gif|left|200px]]

 {{Structure
|PDB= 1otx |SIZE=350|CAPTION= <scene name='initialview01'>1otx</scene>, resolution 2.70&Aring;
|SITE= 
|LIGAND= <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>
|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] </span>
|GENE= 
|DOMAIN=
|RELATEDENTRY=[[1ecp|1ECP]], [[1a90|1A90]], [[1oty|1OTY]]
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1otx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1otx OCA], [http://www.ebi.ac.uk/pdbsum/1otx PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1otx RCSB]</span>
}}

'''Purine Nucleoside Phosphorylase M64V mutant'''


==Overview==
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.

==About this Structure==
1OTX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OTX 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:[http://www.ncbi.nlm.nih.gov/pubmed/14700625 14700625]
[[Category: Escherichia coli]]
[[Category: Purine-nucleoside phosphorylase]]
[[Category: Single protein]]
[[Category: Allan, P W.]]
[[Category: Anand, R.]]
[[Category: Bennett, E M.]]
[[Category: Ealick, S E.]]
[[Category: Hassan, A E.]]
[[Category: McPherson, D T.]]
[[Category: Parker, W B.]]
[[Category: Secrist, J A.]]
[[Category: Sorscher, E J.]]
[[Category: empty]]
[[Category: pnp]]

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