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4da6

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==Crystal structure of the hexameric purine nucleoside phosphorylase from Bacillus subtilis in complex with ganciclovir==
==Crystal structure of the hexameric purine nucleoside phosphorylase from Bacillus subtilis in complex with ganciclovir==
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<StructureSection load='4da6' size='340' side='right' caption='[[4da6]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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<StructureSection load='4da6' size='340' side='right'caption='[[4da6]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4da6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DA6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DA6 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4da6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DA6 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GA2:9-(1,3-DIHYDROXY-PROPOXYMETHANE)GUANINE'>GA2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br>
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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]] 1.7&#8491;</td></tr>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4d8v|4d8v]], [[4d8x|4d8x]], [[4d8y|4d8y]], [[4d98|4d98]], [[4d9h|4d9h]], [[4da0|4da0]], [[4da7|4da7]], [[4da8|4da8]], [[4dab|4dab]], [[4dae|4dae]], [[4dan|4dan]], [[4dao|4dao]], [[4dar|4dar]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GA2:9-(1,3-DIHYDROXY-PROPOXYMETHANE)GUANINE'>GA2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BSU19630, deoD, punB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1423 Bacillus subtilis])</td></tr>
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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=4da6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da6 OCA], [https://pdbe.org/4da6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4da6 RCSB], [https://www.ebi.ac.uk/pdbsum/4da6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4da6 ProSAT]</span></td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
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</table>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4da6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4da6 RCSB], [http://www.ebi.ac.uk/pdbsum/4da6 PDBsum]</span></td></tr>
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== Function ==
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<table>
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[https://www.uniprot.org/uniprot/DEOD_BACSU DEOD_BACSU] Cleavage of adenosine and its derivatives.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The hexameric purine nucleoside phosphorylase from Bacillus subtilis (BsPNP233) displays great potential to produce nucleoside analogues in industry and can be exploited in the development of new anti-tumor gene therapies. In order to provide structural basis for enzyme and substrates rational optimization, aiming at those applications, the present work shows a thorough and detailed structural description of the binding mode of substrates and nucleoside analogues to the active site of the hexameric BsPNP233. Here we report the crystal structure of BsPNP233 in the apo form and in complex with 11 ligands, including clinically relevant compounds. The crystal structure of six ligands (adenine, 2'deoxyguanosine, aciclovir, ganciclovir, 8-bromoguanosine, 6-chloroguanosine) in complex with a hexameric PNP are presented for the first time. Our data showed that free bases adopt alternative conformations in the BsPNP233 active site and indicated that binding of the co-substrate (2'deoxy)ribose 1-phosphate might contribute for stabilizing the bases in a favorable orientation for catalysis. The BsPNP233-adenosine complex revealed that a hydrogen bond between the 5' hydroxyl group of adenosine and Arg(43*) side chain contributes for the ribosyl radical to adopt an unusual C3'-endo conformation. The structures with 6-chloroguanosine and 8-bromoguanosine pointed out that the Cl(6) and Br(8) substrate modifications seem to be detrimental for catalysis and can be explored in the design of inhibitors for hexameric PNPs from pathogens. Our data also corroborated the competitive inhibition mechanism of hexameric PNPs by tubercidin and suggested that the acyclic nucleoside ganciclovir is a better inhibitor for hexameric PNPs than aciclovir. Furthermore, comparative structural analyses indicated that the replacement of Ser(90) by a threonine in the B. cereus hexameric adenosine phosphorylase (Thr(91)) is responsible for the lack of negative cooperativity of phosphate binding in this enzyme.
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Insights into phosphate cooperativity and influence of substrate modifications on binding and catalysis of hexameric purine nucleoside phosphorylases.,de Giuseppe PO, Martins NH, Meza AN, Dos Santos CR, Pereira HD, Murakami MT PLoS One. 2012;7(9):e44282. Epub 2012 Sep 5. PMID:22957058<ref>PMID:22957058</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Purine nucleoside phosphorylase|Purine nucleoside phosphorylase]]
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*[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bacillus subtilis]]
[[Category: Bacillus subtilis]]
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[[Category: Purine-nucleoside phosphorylase]]
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[[Category: Large Structures]]
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[[Category: Giuseppe, P O.]]
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[[Category: Giuseppe PO]]
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[[Category: Martins, N H.]]
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[[Category: Martins NH]]
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[[Category: Meza, A N.]]
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[[Category: Meza AN]]
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[[Category: Murakami, M T.]]
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[[Category: Murakami MT]]
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[[Category: Phosphorylase/hydrolase-like]]
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[[Category: Transferase]]
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Current revision

Crystal structure of the hexameric purine nucleoside phosphorylase from Bacillus subtilis in complex with ganciclovir

PDB ID 4da6

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