3g3d: Difference between revisions
New page: '''Unreleased structure''' The entry 3g3d is ON HOLD Authors: Liu, Y., Tang, H.L., Bello, A., Poduch, E., Kotra, L., Pai, E. Description: Crystal Structure of Human Orotidine 5'-monoph... |
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==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=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3g3d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G3D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3G3D 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]] 1.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5FU:5-FLUORO-URIDINE-5-MONOPHOSPHATE'>5FU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3g3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g3d OCA], [https://pdbe.org/3g3d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3g3d RCSB], [https://www.ebi.ac.uk/pdbsum/3g3d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3g3d ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/UMPS_HUMAN UMPS_HUMAN] Defects in UMPS are the cause of orotic aciduria type 1 (ORAC1) [MIM:[https://omim.org/entry/258900 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.<ref>PMID:9042911</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/UMPS_HUMAN UMPS_HUMAN] | |||
== 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/g3/3g3d_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3g3d ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A 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<ref>PMID:19260677</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3g3d" style="background-color:#fffaf0;"></div> | |||
'' | ==See Also== | ||
*[[Uridine 5'-monophosphate synthase 3D structures|Uridine 5'-monophosphate synthase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Bello A]] | |||
[[Category: Kotra L]] | |||
[[Category: Liu Y]] | |||
[[Category: Pai E]] | |||
[[Category: Poduch E]] | |||
[[Category: Tang HL]] | |||