3sh2

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)

Structural highlights 3sh2 is a 2 chain structure with sequence from "micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Related: 3f0s, 3f0q, 3f0b, 3sgy Gene: dfrA, dfrB, folA ("Micrococcus aureus" (Rosenbach 1884) Zopf 1885) Activity: Dihydrofolate reductase, with EC number 1.5.1.3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dihydrofolate reductase

spinqualitylabelsall models 3sh2, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image