1j3k: Difference between revisions

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-[[Image:1j3k.gif|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_1j3k", creates the "Structure Box" on the page.
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-{{STRUCTURE_1j3k|  PDB=1j3k  |  SCENE=  }}
-'''Quadruple mutant (N51I+C59R+S108N+I164L) Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with WR99210, NADPH, and dUMP'''
+==Quadruple mutant (N51I+C59R+S108N+I164L) Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with WR99210, NADPH, and dUMP==
+<StructureSection load='1j3k' size='340' side='right'caption='[[1j3k]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1j3k]] 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=1J3K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1J3K 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]] 2.1&#8491;</td></tr>
+<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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1j3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j3k OCA], [https://pdbe.org/1j3k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1j3k RCSB], [https://www.ebi.ac.uk/pdbsum/1j3k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1j3k ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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]
+== 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/j3/1j3k_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=1j3k ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-==Overview==
+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>
-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.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-J3K is a [[Protein complex]] structure of sequences 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=1J3K OCA].
+</div>
+<div class="pdbe-citations 1j3k" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-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:[http://www.ncbi.nlm.nih.gov/pubmed/12704428 12704428]
+*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Plasmodium falciparum]]
-[[Category: Protein complex]]
+[[Category: Chitnumsub P]]
-[[Category: Chitnumsub, P.]]
+[[Category: Kamchonwongpaisan S]]
-[[Category: Kamchonwongpaisan, S.]]
+[[Category: Sirawaraporn W]]
-[[Category: Sirawaraporn, W.]]
+[[Category: Taylor P]]
-[[Category: Taylor, P.]]
+[[Category: Vanichtanankul J]]
-[[Category: Vanichtanankul, J.]]
+[[Category: Walkinshaw M]]
-[[Category: Walkinshaw, M.]]
+[[Category: Yuthavong Y]]
-[[Category: Yuthavong, Y.]]
+[[Category: Yuvaniyama J]]
-[[Category: Yuvaniyama, J.]]
-[[Category: Bifunctional]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 20:45:52 2008''