View source for 6cxk


==E. coli DHFR substrate complex with Dihydrofolate==
<StructureSection load='6cxk' size='340' side='right'caption='[[6cxk]], [[Resolution|resolution]] 1.11&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6cxk]] 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=6CXK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CXK 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]] 1.108&#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=DHF:DIHYDROFOLIC+ACID'>DHF</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6cxk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cxk OCA], [https://pdbe.org/6cxk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cxk RCSB], [https://www.ebi.ac.uk/pdbsum/6cxk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cxk 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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6cxk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
== References ==
<references/>
__TOC__
</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]]