4u1r

ATP-bound structure of human platelet phosphofructokinase in an R-state, crystal form II

spinqualitylabelsall models 4u1r, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4u1r is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: ATP, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PFKAP_HUMAN Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis. Publication Abstract from PubMed Phosphofructokinase-1 (Pfk) acts as the main control point of flux through glycolysis. It is involved in complex allosteric regulation and Pfk mutations have been linked to cancer development. Whereas the 3D structure and structural basis of allosteric regulation of prokaryotic Pfk has been studied in great detail, our knowledge about the molecular basis of the allosteric behaviour of the more complex mammalian Pfk is still very limited. To characterize the structural basis of allosteric regulation, the subunit interfaces and the functional consequences of modifications in Tarui's disease and cancer, we analysed the physiological homotetramer of human platelet Pfk at up to 2.67 A resolution in two crystal forms. The crystallized enzyme is permanently activated by a deletion of the 22 C-terminal residues. Complex structures with ADP and fructose-6-phosphate (F6P) and with ATP suggest a role of three aspartates in the deprotonation of the OH-nucleophile of F6P and in the co-ordination of the catalytic magnesium ion. Changes at the dimer interface, including an asymmetry observed in both crystal forms, are the primary mechanism of allosteric regulation of Pfk by influencing the F6P-binding site. Whereas the nature of this conformational switch appears to be largely conserved in bacterial, yeast and mammalian Pfk, initiation of these changes differs significantly in eukaryotic Pfk. Crystal structure of human platelet phosphofructokinase-1 locked in an activated conformation.,Kloos M, Bruser A, Kirchberger J, Schoneberg T, Strater N Biochem J. 2015 Aug 1;469(3):421-32. doi: 10.1042/BJ20150251. Epub 2015 Jun 11. PMID:26205495 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphofructokinase 3D structures

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