1oum: Difference between revisions

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New page: left|200px<br /><applet load="1oum" size="450" color="white" frame="true" align="right" spinBox="true" caption="1oum, resolution 2.40Å" /> '''M64V PNP +Talo'''<br...
 
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[[Image:1oum.gif|left|200px]]<br /><applet load="1oum" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1oum, resolution 2.40&Aring;" />
'''M64V PNP +Talo'''<br />


==Overview==
==M64V PNP +Talo==
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.
<StructureSection load='1oum' size='340' side='right'caption='[[1oum]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1oum]] 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=1OUM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OUM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</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>, <scene name='pdbligand=TAL:9-(6-DEOXY-ALPHA-L-TALOFURANOSYL)-6-METHYLPURINE'>TAL</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=1oum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oum OCA], [https://pdbe.org/1oum PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oum RCSB], [https://www.ebi.ac.uk/pdbsum/1oum PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oum 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/ou/1oum_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=1oum ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1OUM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with PO4 and TAL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1OUM OCA].
*[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
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://ispc.weizmann.ac.il//pmbin/getpm?pmid=14700625 14700625]
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Purine-nucleoside phosphorylase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Allan PW]]
[[Category: Allan, P.W.]]
[[Category: Anand R]]
[[Category: Anand, R.]]
[[Category: Bennett EM]]
[[Category: Bennett, E.M.]]
[[Category: Ealick SE]]
[[Category: Ealick, S.E.]]
[[Category: Hassan AE]]
[[Category: Hassan, A.E.]]
[[Category: McPherson DT]]
[[Category: McPherson, D.T.]]
[[Category: Parker WB]]
[[Category: Parker, W.B.]]
[[Category: Secrist JA]]
[[Category: Secrist, J.A.]]
[[Category: Sorscher EJ]]
[[Category: Sorscher, E.J.]]
[[Category: PO4]]
[[Category: TAL]]
[[Category: m64v]]
[[Category: pnp]]
[[Category: talo]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 23:12:48 2007''

Latest revision as of 11:03, 14 February 2024

M64V PNP +TaloM64V PNP +Talo

Structural highlights

1oum is a 3 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.4Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DEOD_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.

See Also

1oum, resolution 2.40Å

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OCA
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