1j3i

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[[Image:1j3i.png|left|200px]]
 
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==Wild-type Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with WR99210, NADPH, and dUMP==
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The line below this paragraph, containing "STRUCTURE_1j3i", creates the "Structure Box" on the page.
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<StructureSection load='1j3i' size='340' side='right'caption='[[1j3i]], [[Resolution|resolution]] 2.33&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1j3i]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J3I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1J3I FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.33&#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=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene>, <scene name='pdbligand=WRA:6,6-DIMETHYL-1-[3-(2,4,5-TRICHLOROPHENOXY)PROPOXY]-1,6-DIHYDRO-1,3,5-TRIAZINE-2,4-DIAMINE'>WRA</scene></td></tr>
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{{STRUCTURE_1j3i| PDB=1j3i | SCENE= }}
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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=1j3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j3i OCA], [https://pdbe.org/1j3i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1j3i RCSB], [https://www.ebi.ac.uk/pdbsum/1j3i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1j3i ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/DRTS_PLAFK DRTS_PLAFK] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP.[HAMAP-Rule:MF_00008]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j3/1j3i_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1j3i ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) is an important target of antimalarial drugs. The efficacy of this class of DHFR-inhibitor drugs is now compromised because of mutations that prevent drug binding yet retain enzyme activity. The crystal structures of PfDHFR-TS from the wild type (TM4/8.2) and the quadruple drug-resistant mutant (V1/S) strains, in complex with a potent inhibitor WR99210, as well as the resistant double mutant (K1 CB1) with the antimalarial pyrimethamine, reveal features for overcoming resistance. In contrast to pyrimethamine, the flexible side chain of WR99210 can adopt a conformation that fits well in the active site, thereby contributing to binding. The single-chain bifunctional PfDHFR-TS has a helical insert between the DHFR and TS domains that is involved in dimerization and domain organization. Moreover, positively charged grooves on the surface of the dimer suggest a function in channeling of substrate from TS to DHFR active sites. These features provide possible approaches for the design of new drugs to overcome antifolate resistance.
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===Wild-type Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with WR99210, NADPH, and dUMP===
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Insights into antifolate resistance from malarial DHFR-TS structures.,Yuvaniyama J, Chitnumsub P, Kamchonwongpaisan S, Vanichtanankul J, Sirawaraporn W, Taylor P, Walkinshaw MD, Yuthavong Y Nat Struct Biol. 2003 May;10(5):357-65. PMID:12704428<ref>PMID:12704428</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 class="pdbe-citations 1j3i" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 12704428 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12704428}}
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==About this Structure==
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[[1j3i]] is a 4 chain structure of [[Dihydrofolate reductase]] with sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J3I OCA].
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==See Also==
==See Also==
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*[[Dihydrofolate reductase]]
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*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:12704428</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Plasmodium falciparum]]
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[[Category: Chitnumsub, P.]]
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[[Category: Chitnumsub P]]
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[[Category: Kamchonwongpaisan, S.]]
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[[Category: Kamchonwongpaisan S]]
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[[Category: Sirawaraporn, W.]]
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[[Category: Sirawaraporn W]]
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[[Category: Taylor, P.]]
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[[Category: Taylor P]]
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[[Category: Vanichtanankul, J.]]
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[[Category: Vanichtanankul J]]
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[[Category: Walkinshaw, M.]]
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[[Category: Walkinshaw M]]
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[[Category: Yuthavong, Y.]]
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[[Category: Yuthavong Y]]
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[[Category: Yuvaniyama, J.]]
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[[Category: Yuvaniyama J]]
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[[Category: Bifunctional]]
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[[Category: Oxidoreductase]]
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[[Category: Transferase]]
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Current revision

Wild-type Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with WR99210, NADPH, and dUMP

PDB ID 1j3i

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