Walter, Patrick; Mechaly, Ariel; Bous, Julien; Haouz, Ahmed; England, Patrick; Lai-Kee-Him, Josephine; Ancelin, Aurelie; Hoos, Sylviane; Baron, Bruno; Trapani, Stefano; Bron, Patrick; Labesse, Gilles; Munier-Lehmann, Helene published the artcile< Structural basis for the allosteric inhibition of UMP kinase from Gram-positive bacteria, a promising antibacterial target>, Recommanded Product: ((2R,3S,4R,5R)-5-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl dihydrogen phosphate, the main research area is allostery; cryo-EM single particle analysis; crystal structure; enzyme regulation; nucleotide metabolism.
Tuberculosis claims significantly more than one million lives each year. A feasible way to face the issue of drug resistance is the development of new antibiotics. Bacterial UMP (UMP) kinase is a promising target for novel antibiotic discovery as it is essential for bacterial survival and has no counterpart in human cells. The UMP kinase from M. tuberculosis is also a model of particular interest for allosteric regulation with two effectors, GTP (pos.) and UTP (neg.). In this study, using X-ray crystallog. and cryo-electron microscopy, we report for the first time a detailed description of the neg. effector UTP-binding site of a typical Gram-pos. behaving UMP kinase. Comparison between this snapshot of low affinity for Mg-ATP with our previous 3D-structure of the GTP-bound complex of high affinity for Mg-ATP led to a better understanding of the cooperative mechanism and the allosteric regulation of UMP kinase. Thermal shift assay and CD experiments corroborate our model of an inhibition by UTP linked to higher flexibility of the Mg-ATP-binding domain. These new structural insights provide valuable knowledge for future drug discovery strategies targeting bacterial UMP kinases.
FEBS Journal published new progress about 58-97-9. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Recommanded Product: ((2R,3S,4R,5R)-5-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl dihydrogen phosphate.
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem