3k2h
From Proteopedia
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| - | [[Image:3k2h.png|left|200px]] | ||
| - | + | ==Co-crystal structure of dihydrofolate reductase/thymidylate synthase from Babesia bovis with dUMP, Pemetrexed and NADP== | |
| + | <StructureSection load='3k2h' size='340' side='right'caption='[[3k2h]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3k2h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Babesia_bovis Babesia bovis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3K2H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3K2H 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]] 2.2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LYA:2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-PENTANEDIOIC+ACID'>LYA</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</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=3k2h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k2h OCA], [https://pdbe.org/3k2h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3k2h RCSB], [https://www.ebi.ac.uk/pdbsum/3k2h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3k2h ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A7ASX7_BABBO A7ASX7_BABBO] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism (By similarity).[PIRNR:PIRNR000389] | ||
| + | == 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/k2/3k2h_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3k2h ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Babesiosis is a tick-borne disease caused by eukaryotic Babesia parasites which are morphologically similar to Plasmodium falciparum, the causative agent of malaria in humans. Like Plasmodium, different species of Babesia are tuned to infect different mammalian hosts, including rats, dogs, horses and cattle. Most species of Plasmodium and Babesia possess an essential bifunctional enzyme for nucleotide synthesis and folate metabolism: dihydrofolate reductase-thymidylate synthase. Although thymidylate synthase is highly conserved across organisms, the bifunctional form of this enzyme is relatively uncommon in nature. The structural characterization of dihydrofolate reductase-thymidylate synthase in Babesia bovis, the causative agent of babesiosis in livestock cattle, is reported here. The apo state is compared with structures that contain dUMP, NADP and two different antifolate inhibitors: pemetrexed and raltitrexed. The complexes reveal modes of binding similar to that seen in drug-resistant malaria strains and point to the utility of applying structural studies with proven cancer chemotherapies towards infectious disease research. | ||
| - | + | Inhibitor-bound complexes of dihydrofolate reductase-thymidylate synthase from Babesia bovis.,Begley DW, Edwards TE, Raymond AC, Smith ER, Hartley RC, Abendroth J, Sankaran B, Lorimer DD, Myler PJ, Staker BL, Stewart LJ Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Sep 1;67(Pt, 9):1070-7. Epub 2011 Aug 16. PMID:21904052<ref>PMID:21904052</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 3k2h" style="background-color:#fffaf0;"></div> | |
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==See Also== | ==See Also== | ||
| - | *[[Dihydrofolate reductase|Dihydrofolate reductase]] | + | *[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]] |
| - | + | == References == | |
| - | + | <references/> | |
| - | == | + | __TOC__ |
| - | < | + | </StructureSection> |
[[Category: Babesia bovis]] | [[Category: Babesia bovis]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
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Current revision
Co-crystal structure of dihydrofolate reductase/thymidylate synthase from Babesia bovis with dUMP, Pemetrexed and NADP
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