3g3d: Difference between revisions
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==Crystal Structure of Human Orotidine 5'-monophosphate Decarboxylase Covalently Modified by 5-fluoro-6-azido-UMP== | ==Crystal Structure of Human Orotidine 5'-monophosphate Decarboxylase Covalently Modified by 5-fluoro-6-azido-UMP== | ||
<StructureSection load='3g3d' size='340' side='right' caption='[[3g3d]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='3g3d' size='340' side='right' caption='[[3g3d]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gi|13960142, OK/SW-cl.21, UMPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gi|13960142, OK/SW-cl.21, UMPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Orotidine-5'-phosphate_decarboxylase Orotidine-5'-phosphate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.23 4.1.1.23] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Orotidine-5'-phosphate_decarboxylase Orotidine-5'-phosphate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.23 4.1.1.23] </span></td></tr> | ||
<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=3g3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g3d OCA], [http://pdbe.org/3g3d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3g3d RCSB], [http://www.ebi.ac.uk/pdbsum/3g3d PDBsum]</span></td></tr> | <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=3g3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g3d OCA], [http://pdbe.org/3g3d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3g3d RCSB], [http://www.ebi.ac.uk/pdbsum/3g3d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3g3d ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g3/3g3d_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g3/3g3d_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
Revision as of 10:54, 5 December 2018
Crystal Structure of Human Orotidine 5'-monophosphate Decarboxylase Covalently Modified by 5-fluoro-6-azido-UMPCrystal Structure of Human Orotidine 5'-monophosphate Decarboxylase Covalently Modified by 5-fluoro-6-azido-UMP
Structural highlights
Disease[UMPS_HUMAN] Defects in UMPS are the cause of orotic aciduria type 1 (ORAC1) [MIM:258900]. A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. A minority of cases have additional features, particularly congenital malformations and immune deficiencies.[1] 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 PubMedA series of 6-substituted and 5-fluoro-6-substituted uridine derivatives were synthesized and evaluated for their potential as anticancer agents. The designed molecules were synthesized from either fully protected uridine or the corresponding 5-fluorouridine derivatives. The mononucleotide derivatives were used for enzyme inhibition investigations against ODCase. Anticancer activities of all the synthesized derivatives were evaluated using the nucleoside forms of the inhibitors. 5-Fluoro-UMP was a very weak inhibitor of ODCase. 6-Azido-5-fluoro and 5-fluoro-6-iodo derivatives are covalent inhibitors of ODCase, and the active site Lys145 residue covalently binds to the ligand after the elimination of the 6-substitution. Among the synthesized nucleoside derivatives, 6-azido-5-fluoro, 6-amino-5-fluoro, and 6-carbaldehyde-5-fluoro derivatives showed potent anticancer activities in cell-based assays against various leukemia cell lines. On the basis of the overall profile, 6-azido-5-fluoro and 6-amino-5-fluoro uridine derivatives exhibited potential for further investigations. Structure-activity relationships of orotidine-5'-monophosphate decarboxylase inhibitors as anticancer agents.,Bello AM, Konforte D, Poduch E, Furlonger C, Wei L, Liu Y, Lewis M, Pai EF, Paige CJ, Kotra LP J Med Chem. 2009 Mar 26;52(6):1648-58. PMID:19260677[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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