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| | <StructureSection load='5jg0' size='340' side='right'caption='[[5jg0]], [[Resolution|resolution]] 1.88Å' scene=''> | | <StructureSection load='5jg0' size='340' side='right'caption='[[5jg0]], [[Resolution|resolution]] 1.88Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jg0]] is a 1 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=5JG0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JG0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jg0]] is a 1 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=5JG0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JG0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=UC9:4-{6-[(2S)-4-(2,4-DIAMINO-6-ETHYLPYRIMIDIN-5-YL)BUT-3-YN-2-YL]-2H-1,3-BENZODIOXOL-4-YL}BENZOIC+ACID'>UC9</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]] 1.879Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">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>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=UC9:4-{6-[(2S)-4-(2,4-DIAMINO-6-ETHYLPYRIMIDIN-5-YL)BUT-3-YN-2-YL]-2H-1,3-BENZODIOXOL-4-YL}BENZOIC+ACID'>UC9</scene></td></tr> |
| - | <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>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5jg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jg0 OCA], [https://pdbe.org/5jg0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jg0 RCSB], [https://www.ebi.ac.uk/pdbsum/5jg0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jg0 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=5jg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jg0 OCA], [http://pdbe.org/5jg0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jg0 RCSB], [http://www.ebi.ac.uk/pdbsum/5jg0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jg0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Dihydrofolate reductase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Anderson, A C]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Reeve, S M]] | + | [[Category: Anderson AC]] |
| - | [[Category: Antibiotic]] | + | [[Category: Reeve SM]] |
| - | [[Category: Nadph]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Zwitterion]]
| + | |
| Structural highlights
Function
DYR_STAAU Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
Publication Abstract from PubMed
Antibiotic resistance is a rapidly evolving health concern that requires a sustained effort to understand mechanisms of resistance and to develop new agents that overcome those mechanisms. The dihydrofolate reductase (DHFR) inhibitor, trimethoprim (TMP), remains one of the most important orally administered antibiotics. However, resistance through chromosomal mutations and mobile, plasmid-encoded insensitive DHFRs threatens the continued use of this agent. We are pursuing the development of new propargyl-linked antifolate (PLA) DHFR inhibitors designed to evade these mechanisms. While analyzing contemporary TMP-resistant clinical isolates of methicillin-resistant and sensitive Staphylococcus aureus, we discovered two mobile resistance elements, dfrG and dfrK. This is the first identification of these resistance mechanisms in the United States. These resistant organisms were isolated from a variety of infection sites, show clonal diversity, and each contain distinct resistance genotypes for common antibiotics. Several PLAs showed significant activity against these resistant strains by direct inhibition of the TMP resistance elements.
MRSA Isolates from United States Hospitals Carry dfrG and dfrK Resistance Genes and Succumb to Propargyl-Linked Antifolates.,Reeve SM, Scocchera EW, G-Dayanadan N, Keshipeddy S, Krucinska J, Hajian B, Ferreira J, Nailor M, Aeschlimann J, Wright DL, Anderson AC Cell Chem Biol. 2016 Dec 22;23(12):1458-1467. doi:, 10.1016/j.chembiol.2016.11.007. Epub 2016 Dec 8. PMID:27939900[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Reeve SM, Scocchera EW, G-Dayanadan N, Keshipeddy S, Krucinska J, Hajian B, Ferreira J, Nailor M, Aeschlimann J, Wright DL, Anderson AC. MRSA Isolates from United States Hospitals Carry dfrG and dfrK Resistance Genes and Succumb to Propargyl-Linked Antifolates. Cell Chem Biol. 2016 Dec 22;23(12):1458-1467. doi:, 10.1016/j.chembiol.2016.11.007. Epub 2016 Dec 8. PMID:27939900 doi:http://dx.doi.org/10.1016/j.chembiol.2016.11.007
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