6ayu

Crystal structure of fructose-1,6-bisphosphatase T84S from Mycobacterium tuberculosis

spinqualitylabelsall models 6ayu, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ayu is a 2 chain structure with sequence from Mycobacterium tuberculosis H37Ra. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: F6P, GOL, MG, MLI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GLPX_MYCTU Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate (PubMed:15470127, PubMed:21451980). Seems to be the major FBPase of M.tuberculosis and to play a key role in gluconeogenesis for conversion of lipid carbon into cell wall glycans. Does not display activity against inositol 1-phosphate (PubMed:15470127). Publication Abstract from PubMed The crystal structures of native class II fructose-1,6-bisphosphatase (FBPaseII) from Mycobacterium tuberculosis at 2.6 A resolution and two active-site protein variants are presented. The variants were complexed with the reaction product fructose 6-phosphate (F6P). The Thr84Ala mutant is inactive, while the Thr84Ser mutant has a lower catalytic activity. The structures reveal the presence of a 222 tetramer, similar to those described for fructose-1,6/sedoheptulose-1,7-bisphosphatase from Synechocystis (strain 6803) as well as the equivalent enzyme from Thermosynechococcus elongatus. This homotetramer corresponds to a homologous oligomer that is present but not described in the crystal structure of FBPaseII from Escherichia coli and is probably conserved in all FBPaseIIs. The constellation of amino-acid residues in the active site of FBPaseII from M. tuberculosis (MtFBPaseII) is conserved and is analogous to that described previously for the E. coli enzyme. Moreover, the structure of the active site of the partially active (Thr84Ser) variant and the analysis of the kinetics are consistent with the previously proposed catalytic mechanism. The presence of metabolites in the crystallization medium (for example citrate and malonate) and in the corresponding crystal structures of MtFBPaseII, combined with their observed inhibitory effect, could suggest the existence of an uncharacterized inhibition of this class of enzymes besides the allosteric inhibition by adenosine monophosphate observed for the Synechocystis enzyme. The structural and functional insights derived from the structure of MtFBPaseII will provide critical information for the design of lead inhibitors, which will be used to validate this target for future chemical intervention. Structures of the Mycobacterium tuberculosis GlpX protein (class II fructose-1,6-bisphosphatase): implications for the active oligomeric state, catalytic mechanism and citrate inhibition.,Wolf NM, Gutka HJ, Movahedzadeh F, Abad-Zapatero C Acta Crystallogr D Struct Biol. 2018 Apr 1;74(Pt 4):321-331. doi:, 10.1107/S2059798318002838. Epub 2018 Apr 3. PMID:29652259 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Fructose-1%2C6-bisphosphatase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA