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3sh2

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==Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and 6-ethyl-5-(3-(4-methoxybiphenyl-3-yl)prop-1-ynyl)pyrimidine-2,4-diamine (UCP120J)==
==Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and 6-ethyl-5-(3-(4-methoxybiphenyl-3-yl)prop-1-ynyl)pyrimidine-2,4-diamine (UCP120J)==
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<StructureSection load='3sh2' size='340' side='right' caption='[[3sh2]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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<StructureSection load='3sh2' size='340' side='right'caption='[[3sh2]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3sh2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SH2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SH2 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3sh2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SH2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SH2 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=5DR:6-ETHYL-5-[3-(4-METHOXYBIPHENYL-3-YL)PROP-1-YN-1-YL]PYRIMIDINE-2,4-DIAMINE'>5DR</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.999&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3f0s|3f0s]], [[3f0q|3f0q]], [[3f0b|3f0b]], [[3sgy|3sgy]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5DR:6-ETHYL-5-[3-(4-METHOXYBIPHENYL-3-YL)PROP-1-YN-1-YL]PYRIMIDINE-2,4-DIAMINE'>5DR</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dfrA, dfrB, folA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3sh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sh2 OCA], [https://pdbe.org/3sh2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sh2 RCSB], [https://www.ebi.ac.uk/pdbsum/3sh2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sh2 ProSAT]</span></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=3sh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sh2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sh2 RCSB], [http://www.ebi.ac.uk/pdbsum/3sh2 PDBsum]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/DYR_STAAU DYR_STAAU] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
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Hospital- and community-acquired, complicated skin and soft tissue infections, often attributed to Staphylococcus aureus and Streptococcus pyogenes, present a significant health burden that is associated with increased health care costs and mortality. As these two species are difficult to discern on diagnosis and are associated with differential profiles of drug resistance, the development of an efficacious antibacterial agent that targets both organisms is a high priority. Herein we describe a structure-based drug development effort that has produced highly potent inhibitors of dihydrofolate reductase from both species. Optimized propargyl-linked antifolates containing a key pyridyl substituent display antibacterial activity against both methicillin-resistant S. aureus and S. pyogenes at MIC values below 0.1 microg/mL and minimal cytotoxicity against mammalian cells. Further evaluation against a panel of clinical isolates shows good efficacy against a range of important phenotypes such as hospital- and community-acquired strains as well as strains resistant to vancomycin.
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Toward New Therapeutics for Skin and Soft Tissue Infections: Propargyl-Linked Antifolates Are Potent Inhibitors of MRSA and Streptococcus pyogenes.,Viswanathan K, Frey KM, Scocchera EW, Martin BD, Swain Iii PW, Alverson JB, Priestley ND, Anderson AC, Wright DL PLoS One. 2012;7(2):e29434. Epub 2012 Feb 7. PMID:22347365<ref>PMID:22347365</ref>
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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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==See Also==
==See Also==
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*[[Dihydrofolate reductase|Dihydrofolate reductase]]
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*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Dihydrofolate reductase]]
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[[Category: Large Structures]]
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[[Category: Anderson, A C]]
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[[Category: Staphylococcus aureus]]
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[[Category: Frey, K M]]
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[[Category: Anderson AC]]
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[[Category: Nadp]]
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[[Category: Frey KM]]
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[[Category: Nadph]]
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[[Category: One-carbon metabolism]]
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[[Category: Oxidoreductase]]
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[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
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Current revision

Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and 6-ethyl-5-(3-(4-methoxybiphenyl-3-yl)prop-1-ynyl)pyrimidine-2,4-diamine (UCP120J)

PDB ID 3sh2

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