Structural basis for the feedback regulation of Escherichia coli pantothenate kinase by coenzyme A.

摘要: Abstract Pantothenate kinase (PanK) is a key regulatory enzyme in the coenzyme A (CoA) biosynthetic pathway and catalyzes phosphorylation of pantothenic acid to form phosphopantothenate. CoA feedback inhibitor PanK activity by competitive binding ATP site. The structures Escherichia coli enzyme, complex with nonhydrolyzable analogue ATP, 5′-adenylimido-diphosphate (AMPPNP), or CoA, were determined at 2.6 2.5 A, respectively. Both show that two dimers occupy an asymmetric unit; each subunit has α/β mononucleotide-binding fold extensive antiparallel coiled coil formed long helices along dimerization interface. ligands, AMPPNP associate very different ways, but their phosphate sites overlap, explaining kinetic competition between ATP. Residues Asp127, His177, Arg243 are proposed be involved catalysis, based on modeling pentacoordinate transition state. more potent inhibition compared thioesters, explained tight interaction thiol group side chains aromatic residues, which predicted discriminate against thioesters. structure provides framework for detailed understanding mechanism catalysis regulation PanK.