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< | ==Purine Nucleoside Phosphorylase M64V mutant== | ||
<StructureSection load='1otx' size='340' side='right'caption='[[1otx]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1otx]] 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=1OTX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OTX FirstGlance]. <br> | |||
or | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> | ||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1otx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1otx OCA], [https://pdbe.org/1otx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1otx RCSB], [https://www.ebi.ac.uk/pdbsum/1otx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1otx ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ot/1otx_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=1otx ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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<ref>PMID:14700625</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1otx" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
< | |||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Allan | [[Category: Allan PW]] | ||
[[Category: Anand | [[Category: Anand R]] | ||
[[Category: Bennett | [[Category: Bennett EM]] | ||
[[Category: Ealick | [[Category: Ealick SE]] | ||
[[Category: Hassan | [[Category: Hassan AE]] | ||
[[Category: McPherson | [[Category: McPherson DT]] | ||
[[Category: Parker | [[Category: Parker WB]] | ||
[[Category: Secrist | [[Category: Secrist JA]] | ||
[[Category: Sorscher | [[Category: Sorscher EJ]] | ||
Latest revision as of 12:32, 16 August 2023
Purine Nucleoside Phosphorylase M64V mutantPurine Nucleoside Phosphorylase M64V mutant
Structural highlights
FunctionDEOD_ECOLI Cleavage of guanosine or inosine to respective bases and sugar-1-phosphate molecules.[HAMAP-Rule:MF_01627] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedActivation 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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