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5ecc
From Proteopedia
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ecc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ecc OCA], [http://pdbe.org/5ecc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ecc RCSB], [http://www.ebi.ac.uk/pdbsum/5ecc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ecc ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ecc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ecc OCA], [http://pdbe.org/5ecc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ecc RCSB], [http://www.ebi.ac.uk/pdbsum/5ecc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ecc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Multidrug-resistant Enterobacteriaceae, notably Escherichia coli and Klebsiella pneumoniae, have become major health concerns worldwide. Resistance to effective therapeutics is often carried by class I and II integrons that can confer insensitivity to carbapenems, extended spectrum beta-lactamases, the antifolate trimethoprim, fluoroquinolones, and aminoglycosides. Specifically of interest to the study here, a prevalent gene (dfrA1) coding for an insensitive dihydrofolate reductase (DHFR) confers 190- or 1000-fold resistance to trimethoprim for K. pneumoniae and E. coli, respectively. Attaining inhibition of both the wild-type and resistant forms of the enzyme is critical for new antifolates. For several years, we have been developing the propargyl-linked antifolates (PLAs) as effective inhibitors against trimethoprim-resistant DHFR enzymes. Here, we show that the PLAs are active against both the wild-type and DfrA1 DHFR proteins. We report two high-resolution crystal structures of DfrA1 bound to potent PLAs. The structure-activity relationships and crystal structures will be critical in driving the design of broadly active inhibitors against wild-type and resistant DHFR. | ||
| + | |||
| + | Crystal Structures of Trimethoprim-Resistant DfrA1 Rationalize Potent Inhibition by Propargyl-Linked Antifolates.,Lombardo MN, G-Dayanandan N, Wright DL, Anderson AC ACS Infect Dis. 2016 Feb 12;2(2):149-56. doi: 10.1021/acsinfecdis.5b00129. Epub, 2016 Jan 4. PMID:27624966<ref>PMID:27624966</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5ecc" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Dihydrofolate reductase|Dihydrofolate reductase]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 06:19, 18 April 2018
Klebsiella pneumoniae DfrA1 complexed with NADPH and 6-ethyl-5-(3-(2-methoxy-5-(pyridin-4-yl)phenyl)prop-1-yn-1-yl)pyrimidine-2,4-diamine
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