1oum: Difference between revisions

Revision as of 04:17, 3 May 2008

M64V PNP +Talo

OverviewOverview

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 StructureAbout this Structure

1OUM 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 Page seeded by OCA on Sat May 3 04:17:54 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1oum.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1oum |SIZE=350|CAPTION= <scene name='initialview01'>1oum</scene>, resolution 2.40&Aring;
+The line below this paragraph, containing "STRUCTURE_1oum", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TAL:9-(6-DEOXY-ALPHA-L-TALOFURANOSYL)-6-METHYLPURINE'>TAL</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|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>
+or leave the SCENE parameter empty for the default display.
-|GENE= DEOD OR PUP OR B4384 OR Z5986 OR ECS5343 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])
+-->
-|DOMAIN=
+{{STRUCTURE_1oum|  PDB=1oum  |  SCENE=  }}
-|RELATEDENTRY=[[1ecp|1ECP]], [[1a9o|1A9O]], [[1otx|1OTX]], [[1oty|1OTY]], [[1ou4|1OU4]], [[1ov6|1OV6]], [[1ovg|1OVG]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1oum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oum OCA], [http://www.ebi.ac.uk/pdbsum/1oum PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1oum RCSB]</span>
-}}
 '''M64V PNP +Talo'''
@@ Line 35: / Line 32: @@
 [[Category: Secrist, J A.]]
 [[Category: Sorscher, E J.]]
-[[Category: m64v]]
+[[Category: M64v]]
-[[Category: pnp]]
+[[Category: Pnp]]
-[[Category: talo]]
+[[Category: Talo]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 04:17:54 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:50:32 2008''