6cw7: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 6cw7 is ON HOLD
+==E. coli DHFR product complex with (6S)-5,6,7,8-TETRAHYDROFOLATE==
+<StructureSection load='6cw7' size='340' side='right'caption='[[6cw7]], [[Resolution|resolution]] 1.03&Aring;' scene=''>
+== Structural highlights ==
+<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.03&#8491;</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='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>
+</table>
+== 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;">
+== Publication Abstract from PubMed ==
+Dihydrofolate 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.
-Authors: Cao, H., Rodrigues, J., Benach, J., Frommelt, A., Morisco, L., Koss, J., Shakhnovich, E., Skolnick, J.
+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<ref>PMID:30564747</ref>
-Description: E. coli DHFR product complex with (6S)-5,6,7,8-TETRAHYDROFOLATE
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Koss, J]]
+<div class="pdbe-citations 6cw7" style="background-color:#fffaf0;"></div>
-[[Category: Morisco, L]]
-[[Category: Frommelt, A]]
+==See Also==
-[[Category: Shakhnovich, E]]
+*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
-[[Category: Rodrigues, J]]
+== References ==
-[[Category: Benach, J]]
+<references/>
-[[Category: Skolnick, J]]
+__TOC__
-[[Category: Cao, H]]
+</StructureSection>
+[[Category: Escherichia coli CFT073]]
+[[Category: Large Structures]]
+[[Category: Benach J]]
+[[Category: Cao H]]
+[[Category: Frommelt A]]
+[[Category: Koss J]]
+[[Category: Morisco L]]
+[[Category: Rodrigues J]]
+[[Category: Shakhnovich E]]
+[[Category: Skolnick J]]