3k45: Difference between revisions

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OCA

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-{{Seed}}
-[[Image:3k45.jpg|left|200px]]
-<!--
+==Alternate Binding Modes Observed for the E- and Z-isomers of 2,4-Diaminofuro[2,3d]pyrimidines as Ternary Complexes with NADPH and Mouse Dihydrofolate Reductase==
-The line below this paragraph, containing "STRUCTURE_3k45", creates the "Structure Box" on the page.
+<StructureSection load='3k45' size='340' side='right'caption='[[3k45]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3k45]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3K45 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3K45 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=51P:5-[(1Z)-2-(2-METHOXYPHENYL)PROP-1-EN-1-YL]FURO[2,3-D]PYRIMIDINE-2,4-DIAMINE'>51P</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
-{{STRUCTURE_3k45|  PDB=3k45  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3k45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k45 OCA], [https://pdbe.org/3k45 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3k45 RCSB], [https://www.ebi.ac.uk/pdbsum/3k45 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3k45 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DYR_MOUSE DYR_MOUSE] Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
+== 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/k4/3k45_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=3k45 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+To optimize dual receptor tyrosine kinase (RTK) and dihydrofolate reductase (DHFR) inhibition, the E- and Z-isomers of 5-[2-(2-methoxyphenyl)prop-1-en-1-yl]furo[2,3-d]pyrimidine-2,4-diamines (1a and 1b) were separated by HPLC and the X-ray crystal structures (2.0 and 1.4A, respectively) with mouse DHFR and NADPH as well as 1b with human DHFR (1.5A) were determined. The E- and Z-isomers adopt different binding modes when bound to mouse DHFR. A series of 2,4-diaminofuro[2,3-d]pyrimidines 2-13 were designed and synthesized using the X-ray crystal structures of 1a and 1b with DHFR to increase their DHFR inhibitory activity. Wittig reactions of appropriate 2-methoxyphenyl ketones with 2,4-diamino-6-chloromethyl furo[2,3-d]pyrimidine afforded the C8-C9 unsaturated compounds 2-7 and catalytic reduction gave the saturated 8-13. Homologation of the C9-methyl analog maintains DHFR inhibitory activity. In addition, inhibition of EGFR and PDGFR-beta were discovered for saturated C9-homologated analogs 9 and 10 that were absent in the saturated C9-methyl analogs.
-===Alternate Binding Modes Observed for the E- and Z-isomers of 2,4-Diaminofuro[2,3d]pyrimidines as Ternary Complexes with NADPH and Mouse Dihydrofolate Reductase===
+Design, synthesis, and X-ray crystal structures of 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors.,Gangjee A, Li W, Lin L, Zeng Y, Ihnat M, Warnke LA, Green DW, Cody V, Pace J, Queener SF Bioorg Med Chem. 2009 Oct 15;17(20):7324-36. Epub 2009 Aug 22. PMID:19748785<ref>PMID:19748785</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3k45" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_19748785}}, adds the Publication Abstract to the page
+*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 19748785 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_19748785}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Large Structures]]
-K45 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3K45 OCA].
-==Reference==
-<ref group="xtra">PMID:19748785</ref><references group="xtra"/>
-[[Category: Dihydrofolate reductase]]
 [[Category: Mus musculus]]
-[[Category: Cody, V.]]
+[[Category: Cody V]]
-[[Category: Nadp]]
-[[Category: One-carbon metabolism]]
-[[Category: Oxidoreductase]]
-[[Category: Protein ligand cofactor ternary complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 14 10:20:11 2009''