3nu0: Difference between revisions
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==Design, Synthesis, Biological Evaluation and X-ray Crystal Structure of Novel Classical 6,5,6-TricyclicBenzo[4,5]thieno[2,3-d]pyrimidines as Dual Thymidylate Synthase and Dihydrofolate Reductase Inhibitors== | ==Design, Synthesis, Biological Evaluation and X-ray Crystal Structure of Novel Classical 6,5,6-TricyclicBenzo[4,5]thieno[2,3-d]pyrimidines as Dual Thymidylate Synthase and Dihydrofolate Reductase Inhibitors== | ||
<StructureSection load='3nu0' size='340' side='right' caption='[[3nu0]], [[Resolution|resolution]] 1.35Å' scene=''> | <StructureSection load='3nu0' size='340' side='right'caption='[[3nu0]], [[Resolution|resolution]] 1.35Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3nu0]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3nu0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NU0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NU0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3TU:(2S)-2-(5-{[(2-AMINO-4-OXO-3,4-DIHYDRO[1]BENZOTHIENO[2,3-D]PYRIMIDIN-5-YL)METHYL]AMINO}-1-OXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)PENTANEDIOIC+ACID'>3TU</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3TU:(2S)-2-(5-{[(2-AMINO-4-OXO-3,4-DIHYDRO[1]BENZOTHIENO[2,3-D]PYRIMIDIN-5-YL)METHYL]AMINO}-1-OXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)PENTANEDIOIC+ACID'>3TU</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ghc|3ghc]], [[3ntz|3ntz]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ghc|3ghc]], [[3ntz|3ntz]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DHFR, DHFRP1 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DHFR, DHFRP1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3nu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nu0 OCA], [https://pdbe.org/3nu0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nu0 RCSB], [https://www.ebi.ac.uk/pdbsum/3nu0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nu0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
[[ | [[https://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Defects in DHFR are the cause of megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:[https://omim.org/entry/613839 613839]]. DHFRD is an inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.<ref>PMID:21310276</ref> <ref>PMID:21310277</ref> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] 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.<ref>PMID:21876188</ref> <ref>PMID:12096917</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 3nu0" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3nu0" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Dihydrofolate reductase]] | [[Category: Dihydrofolate reductase]] | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Cody, V]] | [[Category: Cody, V]] | ||
[[Category: Cyclized inhibitor]] | [[Category: Cyclized inhibitor]] | ||
[[Category: Oxidoreductase hdhfr-264-nadph]] | [[Category: Oxidoreductase hdhfr-264-nadph]] | ||
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | ||