4or7

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'''Unreleased structure'''
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==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==
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<StructureSection load='4or7' size='340' side='right' caption='[[4or7]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4or7]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OR7 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4osg|4osg]]</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>
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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=4or7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4or7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4or7 RCSB], [http://www.ebi.ac.uk/pdbsum/4or7 PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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The entry 4or7 is ON HOLD until Paper Publication
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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>
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Authors: Lamb, K.M., Anderson, A.C.
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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Description: 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
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Dihydrofolate reductase]]
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[[Category: Anderson, A C]]
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[[Category: Lamb, K M]]
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[[Category: 8-dihydrofolate]]
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[[Category: 8-tetrahydrofolate]]
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[[Category: Hydride shift]]
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[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

Revision as of 09:21, 3 December 2014

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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