5ja3

Mycobacterium tuberculosis Dihydrofolate Reductase complexed with beta- NADPH and 3'-(3-(2,4-diamino-6-ethylpyrimidin-5-yl)prop-2-yn-1-yl)-4'-methoxy-[1,1'-b iphenyl]-4-carboxylic acid (UCP1106)Mycobacterium tuberculosis Dihydrofolate Reductase complexed with beta- NADPH and 3'-(3-(2,4-diamino-6-ethylpyrimidin-5-yl)prop-2-yn-1-yl)-4'-methoxy-[1,1'-b iphenyl]-4-carboxylic acid (UCP1106)

Structural highlights 5ja3 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Activity: Dihydrofolate reductase, with EC number 1.5.1.3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DYR_MYCTO] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity). Publication Abstract from PubMed Mycobacterium tuberculosis continues to cause widespread, life-threatening disease. In the last decade, this threat has grown dramatically as multi- and extensively-drug resistant (MDR and XDR) bacteria have spread globally and the number of agents that effectively treat these infections is significantly reduced. We have been developing the propargyl-linked antifolates (PLAs) as potent inhibitors of the essential enzyme dihydrofolate reductase (DHFR) from bacteria and recently found that charged PLAs with partial zwitterionic character showed improved mycobacterial cell permeability. Building on a hypothesis that these PLAs may penetrate the outer membrane of M. tuberculosis and inhibit the essential cytoplasmic DHFR, we screened a group of PLAs for antitubercular activity. In this work, we identified several PLAs as potent inhibitors of the growth of M. tuberculosis with several of the compounds exhibiting minimum inhibition concentrations equal to or less than 1 mug/mL. Furthermore, two of the compounds were very potent inhibitors of MDR and XDR strains. A high resolution crystal structure of one PLA bound to DHFR from M. tuberculosis reveals the interactions of the ligands with the target enzyme. Propargyl-Linked Antifolates Are Potent Inhibitors of Drug-Sensitive and Drug-Resistant Mycobacterium tuberculosis.,Hajian B, Scocchera E, Keshipeddy S, G-Dayanandan N, Shoen C, Krucinska J, Reeve S, Cynamon M, Anderson AC, Wright DL PLoS One. 2016 Aug 31;11(8):e0161740. doi: 10.1371/journal.pone.0161740., eCollection 2016. PMID:27580226 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 5ja3, resolution 1.81Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image