5ofu | pdb_00005ofu

Crystal structure of Leishmania major fructose-1,6-bisphosphatase in T-state.

spinqualitylabelsall models 5ofu, resolution 2.62Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ofu is a 4 chain structure with sequence from Leishmania major. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.62Å Ligands: AMP, CL, F6P Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function O97193_LEIMA Publication Abstract from PubMed The gluconeogenic enzyme fructose-1,6-bisphosphatase has been proposed as a potential drug target against Leishmania parasites that cause up to 20,000-30,000 deaths annually. A comparison of three crystal structures of L. major fructose-1,6-bisphosphatase (LmFBPase) along with enzyme kinetic data show how AMP acts as an allosteric inhibitor and provides insight into its metal-dependent reaction mechanism. The crystal structure of the apoenzyme form of LmFBPase is a homotetramer in which the dimer of dimers adopts a planar conformation with disordered 'dynamic loops'. The structure of LmFBPase, complexed with manganese and its catalytic product phosphate shows the dynamic loops locked into the active sites. A third crystal structure of LmFBPase complexed with its allosteric inhibitor AMP shows an inactive form of the tetramer, in which the dimer pairs are rotated by 18 degrees relative to each other. The three structures suggest an allosteric mechanism in which AMP binding triggers a rearrangement of hydrogen-bonds across the large and small interfaces. Retraction of the 'effector loop' required for AMP binding releases the side chain of His23 from the dimer-dimer interface. This is coupled with a flip of the side chain of Arg48 which ties down the key catalytic dynamic loop in a disengaged conformation and also locks the tetramer in an inactive rotated T-state. The structure of the effector site of LmFBPase shows different structural features compared with human FBPases, thereby offering a potential and species-specific drug target. Structures of Leishmania Fructose-1,6-bisphosphatase Reveal Species-Specific Differences in the Mechanism of Allosteric Inhibition.,Yuan M, Vasquez-Valdivieso MG, McNae I, Michels PAM, Fothergill-Gilmore LA, Walkinshaw MD J Mol Biol. 2017 Sep 4. pii: S0022-2836(17)30416-3. doi:, 10.1016/j.jmb.2017.08.010. PMID:28882541 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Fructose-1%2C6-bisphosphatase 3D structures

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