4hib

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[[Image:4hib.jpg|left|200px]]
 
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{{STRUCTURE_4hib| PDB=4hib | SCENE= }}
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==Crystal structure of human orotidine 5'-monophosphate decarboxylase complexed with CMP-N4-OH==
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<StructureSection load='4hib' size='340' side='right'caption='[[4hib]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4hib]] 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=4HIB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HIB FirstGlance]. <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]] 1.8&#8491;</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=16B:N-HYDROXYCYTIDINE+5-(DIHYDROGEN+PHOSPHATE)'>16B</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=4hib FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hib OCA], [https://pdbe.org/4hib PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hib RCSB], [https://www.ebi.ac.uk/pdbsum/4hib PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hib ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[https://www.uniprot.org/uniprot/UMPS_HUMAN UMPS_HUMAN]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Orotidine-5'-monophosphate decarboxylase (ODCase) is an interesting enzyme with an unusual catalytic activity and a potential drug target in Plasmodium falciparum, which causes malaria. ODCase has been shown to exhibit unusual and interesting interactions with a variety of nucleotide ligands. Cytidine-5'-monophosphate (CMP) is a poor ligand of ODCase, and CMP binds to the active site of ODCase with an unusual orientation and conformation. We designed N3- and N4-modified CMP derivatives as novel ligands to ODCase. These novel CMP derivatives and their corresponding nucleosides were evaluated against Plasmodium falciparum ODCase and parasitic cultures, respectively. These derivatives exhibited improved inhibition of the enzyme catalytic activity, displayed interesting binding conformations and unusual molecular rearrangements of the ligands. These findings with the modified CMP nucleotides underscored the potential of transformation of poor ligands to ODCase into novel inhibitors of this drug target.
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===Crystal structure of human orotidine 5'-monophosphate decarboxylase complexed with CMP-N4-OH===
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Novel cytidine-based orotidine-5'-monophosphate decarboxylase inhibitors with an unusual twist.,Purohit MK, Poduch E, Wei LW, Crandall IE, To T, Kain KC, Pai EF, Kotra LP J Med Chem. 2012 Nov 26;55(22):9988-97. doi: 10.1021/jm301176r. Epub 2012 Oct 18. PMID:22991951<ref>PMID:22991951</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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<div class="pdbe-citations 4hib" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[4hib]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HIB OCA].
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*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
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*[[Uridine 5'-monophosphate synthase 3D structures|Uridine 5'-monophosphate synthase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Orotidine-5'-phosphate decarboxylase]]
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[[Category: Large Structures]]
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[[Category: Kotra, L P.]]
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[[Category: Kotra LP]]
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[[Category: Pai, E F.]]
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[[Category: Pai EF]]
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[[Category: To, T K.]]
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[[Category: To TK]]
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[[Category: Alpa-beta barrel]]
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[[Category: Decarboxylase]]
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[[Category: Lyase-lyase inhibitor complex]]
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[[Category: Tim barrel]]
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Current revision

Crystal structure of human orotidine 5'-monophosphate decarboxylase complexed with CMP-N4-OH

PDB ID 4hib

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