HUMAN PYRIDOXAL KINASE - CDNA CLONING, EXPRESSION, AND MODULATION BY LIGANDS OF THE BENZODIAZEPINE RECEPTOR

Peptide fragments of a porcine benzodiazepine-binding protein were use d to isolate the cDNA of a related human protein. The cDNA encodes a p olypeptide of 312 amino acid residues that is homologous to a bacteria l pyridoxal kinase. Transient expression of the cDNA in human embryoni c kidney cells confirmed that it encodes human pyridoxal kinase. The r ecombinant enzyme displayed a Rm value of 3.3 mu M for pyridoxal and w as inhibited competitively by 4-deoxypyridoxine (K-i = 2.8 mu M). Benz odiazepine receptor ligands that bound to the purified porcine protein also exerted a potent inhibitory effect on human pyridoxal kinase act ivity. Transcripts of the pyridoxal kinase gene were detectable in all human tissues examined, and were particularly abundant in the testes. The gene is localized on chromo some 21q22.3 and represents a candida te gene for at least one genetic disorder that has been mapped to this region (autoimmune polyglandular disease type 1).