4or7: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4or7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae_CG43 Klebsiella pneumoniae CG43]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OR7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OR7 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4or7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae_CG43 Klebsiella pneumoniae CG43]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OR7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OR7 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=25U:6-ETHYL-5-{3-[3-(PYRIMIDIN-5-YL)PHENYL]PROP-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>25U</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.76&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=25U:6-ETHYL-5-{3-[3-(PYRIMIDIN-5-YL)PHENYL]PROP-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>25U</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=4or7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4or7 OCA], [https://pdbe.org/4or7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4or7 RCSB], [https://www.ebi.ac.uk/pdbsum/4or7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4or7 ProSAT]</span></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=4or7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4or7 OCA], [https://pdbe.org/4or7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4or7 RCSB], [https://www.ebi.ac.uk/pdbsum/4or7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4or7 ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Resistance to the antibacterial antifolate trimethoprim (TMP) is increasing in members of the family Enterobacteriaceae, driving the design of next-generation antifolates effective against these Gram-negative pathogens. The propargyl-linked antifolates are potent inhibitors of dihydrofolate reductases (DHFR) from several TMP-sensitive and -resistant species, including Klebsiella pneumoniae. Recently, we have determined that these antifolates inhibit the growth of strains of K. pneumoniae, some with MIC values of 1 mug/ml. In order to further the design of potent and selective antifolates against members of the Enterobacteriaceae, we determined the first crystal structures of K. pneumoniae DHFR bound to two of the propargyl-linked antifolates. These structures highlight that interactions with Leu 28, Ile 50, Ile 94, and Leu 54 are necessary for potency; comparison with structures of human DHFR bound to the same inhibitors reveal differences in residues (N64E, P61G, F31L, and V115I) and loop conformations (residues 49 to 53) that may be exploited for selectivity.
Crystal Structures of Klebsiella pneumoniae Dihydrofolate Reductase Bound to Propargyl-Linked Antifolates Reveal Features for Potency and Selectivity.,Lamb KM, Lombardo MN, Alverson J, Priestley ND, Wright DL, Anderson AC Antimicrob Agents Chemother. 2014 Dec;58(12):7484-91. doi: 10.1128/AAC.03555-14. , Epub 2014 Oct 6. PMID:25288083<ref>PMID:25288083</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4or7" style="background-color:#fffaf0;"></div>


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

Latest revision as of 12:41, 1 March 2024

Klebsiella pneumoniae dihydrofolate reductase complexed with NADPH and 6-ethyl-5-{3-[3-(pyrimidin-5-yl)phenyl]prop-1-yn-1-yl}pyrimidine-2,4-diamine

4or7, resolution 1.76Å

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