7bl7

Crystal structure of UMPK from M. tuberculosis in complex with UDP and UTP (P21212 form)

spinqualitylabelsall models 7bl7, resolution 3.33Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7bl7 is a 12 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.33Å Ligands: UDP, UTP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PYRH_MYCTU Catalyzes the reversible phosphorylation of UMP to UDP.[HAMAP-Rule:MF_01220] Publication Abstract from PubMed 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 uridine 5'-monophosphate (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 (positive) and UTP (negative). In this study, using X-ray crystallography and cryo-electron microscopy, we report for the first time a detailed description of the negative effector UTP-binding site of a typical Gram-positive 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 circular dichroism 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. Structural basis for the allosteric inhibition of UMP kinase from Gram-positive bacteria, a promising antibacterial target.,Walter P, Mechaly A, Bous J, Haouz A, England P, Lai-Kee-Him J, Ancelin A, Hoos S, Baron B, Trapani S, Bron P, Labesse G, Munier-Lehmann H FEBS J. 2022 Feb 12. doi: 10.1111/febs.16393. PMID:35152545 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Uridylate kinase

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