Activation of biliverdin-IX{alpha} reductase by inorganic phosphate and related anions

Edward Franklin (1) , Seamus Browne , Jerrard Hayes , Coilin Boland , Aisling Dunne , Gordon Elliot , Timothy Mantle

1 School of Biochemistry and Immunology

The effect of pH on the initial rate kinetic behaviour of BVR-A exhibits an alkaline optimum with reduced nicotinamide adenine dinucleotide phosphate as cofactor but a neutral optimum with reduced nicotinamide adenine dinucleotide as cofactor. This has been described as 'dual cofactor and dual pH dependent' behaviour however no mechanism has been described to explain this phenomenon. We present evidence that the apparent peak of activity at neutral pH seen with phosphate buffer and reduced nicotinamide adenine dinucleotide as cofactor is an anion-dependent activation where inorganic phosphate apparently mimicks the role played by the 2'-phosphate of reduced nicotinamide adenine dinucleotide phosphate in stabilising the interaction between reduced nicotinamide adenine dinucleotide and the enzyme. The enzymes from mouse, rat and human all exhibit this behaviour. This behaviour is not seen with biliverdin-IXα reductase from Xenopus tropicalis or the ancient cyanobacterial enzyme from Synechocystis PCC 6803 which, in addition to being refractory to activation by inorganic phosphate, is also differentiated by an acid pH optimum with both pyridine nucleotides.

Mots clés: Life Sciences

Edward Franklin, Seamus Browne, Jerrard Hayes, Coilin Boland, Aisling Dunne, et al.. Activation of biliverdin-IX{alpha} reductase by inorganic phosphate and related anions. Biochemical Journal, 2007, 405 (1), pp.61-67. ⟨10.1042/BJ20061651⟩. ⟨hal-00478691⟩