6cw7: Difference between revisions
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<StructureSection load='6cw7' size='340' side='right'caption='[[6cw7]], [[Resolution|resolution]] 1.03Å' scene=''> | <StructureSection load='6cw7' size='340' side='right'caption='[[6cw7]], [[Resolution|resolution]] 1.03Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6cw7]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6cw7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_CFT073 Escherichia coli CFT073]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CW7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CW7 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]] 1.03Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=THG:(6S)-5,6,7,8-TETRAHYDROFOLATE'>THG</scene></td></tr> | |||
<tr id=' | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6cw7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cw7 OCA], [https://pdbe.org/6cw7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cw7 RCSB], [https://www.ebi.ac.uk/pdbsum/6cw7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cw7 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 CFT073]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Benach | [[Category: Benach J]] | ||
[[Category: Cao | [[Category: Cao H]] | ||
[[Category: Frommelt | [[Category: Frommelt A]] | ||
[[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]] | ||
Latest revision as of 18:12, 4 October 2023
E. coli DHFR product complex with (6S)-5,6,7,8-TETRAHYDROFOLATEE. coli DHFR product complex with (6S)-5,6,7,8-TETRAHYDROFOLATE
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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