7r6g

<StructureSection load='7r6g' size='340' side='right'caption='[[7r6g]], [[Resolution|resolution]] 2.61&Aring;' scene=''>

<table><tr><td colspan='2'>[[7r6g]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R6G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R6G FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TOP:TRIMETHOPRIM'>TOP</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=7r6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r6g OCA], [https://pdbe.org/7r6g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r6g RCSB], [https://www.ebi.ac.uk/pdbsum/7r6g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r6g ProSAT]</span></td></tr>

== Function ==

[[https://www.uniprot.org/uniprot/DYR5_ECOLX DYR5_ECOLX]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

Two plasmid-encoded dihydrofolate reductase (DHFR) isoforms, DfrA1 and DfrA5, that give rise to high levels of resistance in Gram-negative bacteria were structurally and biochemically characterized to reveal the mechanism of TMP resistance and to support phylogenic groupings for drug development against antibiotic resistant pathogens. Preliminary screening of novel antifolates revealed related chemotypes that showed high levels of inhibitory potency against Escherichia coli chromosomal DHFR (EcDHFR), DfrA1, and DfrA5. Kinetics and biophysical analysis, coupled with crystal structures of trimethoprim bound to EcDHFR, DfrA1 and DfrA5, and two propargyl-linked antifolates (PLA) complexed with EcDHFR, DfrA1 and DfrA5, were determined to define structural features of the substrate binding pocket and guide synthesis of pan-DHFR inhibitors.

Structure-guided functional studies of plasmid-encoded dihydrofolate reductases reveal a common mechanism of trimethoprim resistance in Gram-negative pathogens.,Krucinska J, Lombardo MN, Erlandsen H, Estrada A, Si D, Viswanathan K, Wright DL Commun Biol. 2022 May 13;5(1):459. doi: 10.1038/s42003-022-03384-y. PMID:35562546<ref>PMID:35562546</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

</div>

<div class="pdbe-citations 7r6g" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Dihydrofolate reductase]]

[[Category: Estrada, A]]

[[Category: Krucinska, J]]

[[Category: Wright, D]]

[[Category: Oxidoreductase]]