1otx

From Proteopedia

(Difference between revisions)

Current revision

Purine Nucleoside Phosphorylase M64V mutant

Structural highlights

1otx 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 2.7Å
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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. Designer gene therapy using an Escherichia coli purine nucleoside phosphorylase/prodrug system. Chem Biol. 2003 Dec;10(12):1173-81. PMID:14700625

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1otx"

@@ Line 3: / Line 3: @@
 <StructureSection load='1otx' size='340' side='right'caption='[[1otx]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1otx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. 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>
+<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>
-</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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ecp|1ecp]], [[1a90|1a90]], [[1oty|1oty]]</div></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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] </span></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]
+[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]]
@@ Line 37: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Bacillus coli migula 1895]]
+[[Category: Escherichia coli]]
 [[Category: Large Structures]]
-[[Category: Purine-nucleoside phosphorylase]]
+[[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: Empty]]
-[[Category: Pnp]]
-[[Category: Transferase]]

1otx

From Proteopedia

Current revision

Purine Nucleoside Phosphorylase M64V mutant

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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