1ou4

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[[Image:1ou4.jpg|left|200px]]
 
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{{Structure
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==Native PNP +Talo==
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|PDB= 1ou4 |SIZE=350|CAPTION= <scene name='initialview01'>1ou4</scene>, resolution 2.50&Aring;
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<StructureSection load='1ou4' size='340' side='right'caption='[[1ou4]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene> and <scene name='pdbligand=6MP:6-METHYLPURINE'>6MP</scene>
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<table><tr><td colspan='2'>[[1ou4]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OU4 FirstGlance]. <br>
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|ACTIVITY= [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]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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|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])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6MP:6-METHYLPURINE'>6MP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ou4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ou4 OCA], [https://pdbe.org/1ou4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ou4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ou4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ou4 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/DEOD_ECOLI DEOD_ECOLI] Cleavage of guanosine or inosine to respective bases and sugar-1-phosphate molecules.[HAMAP-Rule:MF_01627]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ou/1ou4_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ou4 ConSurf].
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<div style="clear:both"></div>
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'''Native PNP +Talo'''
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==See Also==
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*[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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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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==About this Structure==
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1OU4 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=1OU4 OCA].
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==Reference==
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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]
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[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: Purine-nucleoside phosphorylase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Allan PW]]
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[[Category: Allan, P W.]]
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[[Category: Anand R]]
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[[Category: Anand, R.]]
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[[Category: Bennett EM]]
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[[Category: Bennett, E M.]]
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[[Category: Ealick SE]]
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[[Category: Ealick, S E.]]
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[[Category: Hassan AE]]
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[[Category: Hassan, A E.]]
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[[Category: McPherson DT]]
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[[Category: McPherson, D T.]]
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[[Category: Parker WB]]
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[[Category: Parker, W B.]]
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[[Category: Secrist JA]]
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[[Category: Secrist, J A.]]
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[[Category: Sorscher EJ]]
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[[Category: Sorscher, E J.]]
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[[Category: 6MP]]
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[[Category: PO4]]
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[[Category: native]]
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[[Category: talo]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:15:36 2008''
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Current revision

Native PNP +Talo

PDB ID 1ou4

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