5tle

Fructose-1,6-bisphosphate aldolase from rabbit muscle in complex with the inhibitor 2-phosphate-naphthalene 6-bisphosphonate

spinqualitylabelsall models 5tle, resolution 1.58Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5tle is a 4 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.576Å Ligands: GOL, RD1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ALDOA_RABIT Plays a key role in glycolysis and gluconeogenesis. In addition, may also function as scaffolding protein. Publication Abstract from PubMed The glycolytic enzyme aldolase is an emerging drug target in diseases such as cancer and protozoan infections which are dependent on a hyperglycolytic phenotype to synthesize adenosine 5'-triphosphate and metabolic precursors for biomass production. To date, structural information for the enzyme in complex with phosphate-derived inhibitors has been lacking. Thus, we determined the crystal structure of mammalian aldolase in complex with naphthalene 2,6-bisphosphate (1) that served as a template for the design of bisphosphonate-based inhibitors, namely, 2-phosphate-naphthalene 6-bisphosphonate (2), 2-naphthol 6-bisphosphonate (3), and 1-phosphate-benzene 4-bisphosphonate (4). All inhibitors targeted the active site, and the most promising lead, 2, exhibited slow-binding inhibition with an overall inhibition constant of approximately 38 nM. Compound 2 inhibited proliferation of HeLa cancer cells, whereas HEK293 cells expressing a normal phenotype were not inhibited. The crystal structures delineated the essential features of high-affinity phosphate-derived inhibitors and provide a template for the development of inhibitors with prophylaxis potential. Bisphosphonate Inhibitors of Mammalian Glycolytic Aldolase.,Heron PW, Abellan-Flos M, Salmon L, Sygusch J J Med Chem. 2018 Dec 13;61(23):10558-10572. doi: 10.1021/acs.jmedchem.8b01000., Epub 2018 Dec 3. PMID:30418024 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aldolase 3D structures

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