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| | ==Crystal structure of rcl with phospho-triciribine== | | ==Crystal structure of rcl with phospho-triciribine== |
| - | <StructureSection load='4fyh' size='340' side='right' caption='[[4fyh]], [[Resolution|resolution]] 2.44Å' scene=''> | + | <StructureSection load='4fyh' size='340' side='right'caption='[[4fyh]], [[Resolution|resolution]] 2.44Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fyh]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FYH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FYH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fyh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FYH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FYH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TR5:5-METHYL-1-(5-O-PHOSPHONO-BETA-D-RIBOFURANOSYL)-1,5-DIHYDRO-1,4,5,6,8-PENTAAZAACENAPHTHYLEN-3-AMINE'>TR5</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TR5:5-METHYL-1-(5-O-PHOSPHONO-BETA-D-RIBOFURANOSYL)-1,5-DIHYDRO-1,4,5,6,8-PENTAAZAACENAPHTHYLEN-3-AMINE'>TR5</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2klh|2klh]], [[4fyi|4fyi]], [[4fyk|4fyk]]</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=4fyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fyh OCA], [https://pdbe.org/4fyh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fyh RCSB], [https://www.ebi.ac.uk/pdbsum/4fyh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fyh ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rcl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4fyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fyh OCA], [http://pdbe.org/4fyh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fyh RCSB], [http://www.ebi.ac.uk/pdbsum/4fyh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fyh ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DNPH1_RAT DNPH1_RAT]] Catalyzes the cleavage of the N-glycosidic bond of deoxyribonucleoside 5'-monophosphates to yield deoxyribose 5-phosphate and a purine or pyrimidine base. Deoxyribonucleoside 5'-monophosphates containing purine bases are preferred to those containing pyrimidine bases.<ref>PMID:17234634</ref> | + | [https://www.uniprot.org/uniprot/DNPH1_RAT DNPH1_RAT] Catalyzes the cleavage of the N-glycosidic bond of deoxyribonucleoside 5'-monophosphates to yield deoxyribose 5-phosphate and a purine or pyrimidine base. Deoxyribonucleoside 5'-monophosphates containing purine bases are preferred to those containing pyrimidine bases.<ref>PMID:17234634</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Kaminski, P A]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Labesse, G]] | + | [[Category: Kaminski PA]] |
| - | [[Category: Padilla, A]] | + | [[Category: Labesse G]] |
| - | [[Category: Deoxyribonucleoside 5'-monophosphate n-glycosidase]] | + | [[Category: Padilla A]] |
| - | [[Category: Hydrolase-inhibitor complex]]
| + | |
| Structural highlights
Function
DNPH1_RAT Catalyzes the cleavage of the N-glycosidic bond of deoxyribonucleoside 5'-monophosphates to yield deoxyribose 5-phosphate and a purine or pyrimidine base. Deoxyribonucleoside 5'-monophosphates containing purine bases are preferred to those containing pyrimidine bases.[1]
Publication Abstract from PubMed
Rcl is a novel N-glycoside hydrolase found in mammals that shows specificity for the hydrolysis of 5'-monophosphate nucleotides. Its role in nucleotide catabolism and the resulting production of 2-deoxyribose 5-phosphate has suggested that it might fuel cancer growth. Its expression is regulated by c-Myc, but its role as an oncoprotein remains to be clarified. In parallel, various nucleosides have been shown to acquire pro-apoptotic properties upon 5'-monophosphorylation in cells. These include triciribine, a tricyclic nucleoside analogue that is currently in clinical trials in combination with a farnesyltransferase inhibitor. Similarly, an N(6)-alkyl-AMP has been shown to be cytotoxic. Interestingly, Rcl has been shown to be inhibited by such compounds in vitro. In order to gain better insight into the precise ligand-recognition determinants, the crystallization of Rcl with these nucleotide analogues was attempted. The first crystal structure of Rcl was solved by molecular replacement using its NMR structure in combination with distantly related crystal structures. The structures of Rcl bound to two other nucleotides were then solved by molecular replacement using the previous crystal structure as a template. The resulting structures, solved at high resolution, led to a clear characterization of the protein-ligand interactions that will guide further rational drug design.
Structure of the oncoprotein Rcl bound to three nucleotide analogues.,Padilla A, Amiable C, Pochet S, Kaminski PA, Labesse G Acta Crystallogr D Biol Crystallogr. 2013 Feb;69(Pt 2):247-55. doi:, 10.1107/S0907444912045039. Epub 2013 Jan 19. PMID:23385460[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ghiorghi YK, Zeller KI, Dang CV, Kaminski PA. The c-Myc target gene Rcl (C6orf108) encodes a novel enzyme, deoxynucleoside 5'-monophosphate N-glycosidase. J Biol Chem. 2007 Mar 16;282(11):8150-6. Epub 2007 Jan 18. PMID:17234634 doi:http://dx.doi.org/10.1074/jbc.M610648200
- ↑ Padilla A, Amiable C, Pochet S, Kaminski PA, Labesse G. Structure of the oncoprotein Rcl bound to three nucleotide analogues. Acta Crystallogr D Biol Crystallogr. 2013 Feb;69(Pt 2):247-55. doi:, 10.1107/S0907444912045039. Epub 2013 Jan 19. PMID:23385460 doi:http://dx.doi.org/10.1107/S0907444912045039
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