6cqa: Difference between revisions
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<StructureSection load='6cqa' size='340' side='right'caption='[[6cqa]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='6cqa' size='340' side='right'caption='[[6cqa]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6cqa]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6cqa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CQA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CQA FirstGlance]. <br> | ||
</td></tr><tr id=' | </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=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PQD:7-[(3-aminophenyl)methyl]-7H-pyrrolo[3,2-f]quinazoline-1,3-diamine'>PQD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6cqa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cqa OCA], [https://pdbe.org/6cqa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cqa RCSB], [https://www.ebi.ac.uk/pdbsum/6cqa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cqa ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/DYR_ECOLI DYR_ECOLI] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Benach | [[Category: Benach J]] | ||
[[Category: Cao | [[Category: Cao H]] | ||
[[Category: Koss | [[Category: Koss J]] | ||
[[Category: Morisco | [[Category: Morisco L]] | ||
[[Category: Rodrigues | [[Category: Rodrigues J]] | ||
[[Category: Shakhnovich | [[Category: Shakhnovich E]] | ||
[[Category: Skolnick | [[Category: Skolnick J]] | ||
[[Category: Wasserman | [[Category: Wasserman S]] | ||
Latest revision as of 18:09, 4 October 2023
E. coli DHFR complex with inhibitor AMPQDE. coli DHFR complex with inhibitor AMPQD
Structural highlights
FunctionDYR_ECOLI Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Publication Abstract from PubMedDihydrofolate reductase (DHFR) catalyzes the stereospecific reduction of 7,8-dihydrofolate (FH2) to (6s)-5,6,7,8-tetrahydrofolate (FH4) via hydride transfer from NADPH. The consensus Escherichia coli DHFR mechanism involves conformational changes between closed and occluded states occurring during the rate-limiting product release step. Although the Protein Data Bank (PDB) contains over 250 DHFR structures, the FH4 complex structure responsible for rate-limiting product release is unknown. We report to our knowledge the first crystal structure of an E. coli. DHFR:FH4 complex at 1.03 A resolution showing distinct stabilizing interactions absent in FH2 or related (6R)-5,10-dideaza-FH4 complexes. We discover the time course of decay of the co-purified endogenous FH4 during crystal growth, with conversion from FH4 to FH2 occurring in 2-3 days. We also determine another occluded complex structure of E. coli DHFR with a slow-onset nanomolar inhibitor that contrasts with the methotrexate complex, suggesting a plausible strategy for designing DHFR antibiotics by targeting FH4 product conformations. The crystal structure of a tetrahydrofolate-bound dihydrofolate reductase reveals the origin of slow product release.,Cao H, Gao M, Zhou H, Skolnick J Commun Biol. 2018 Dec 12;1:226. doi: 10.1038/s42003-018-0236-y. eCollection 2018. PMID:30564747[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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