Methylenetetrahydrofolate dehydrogenase-cyclohydrolase from Photobacterium phosphoreum shares properties with a mammalian mitochondrial homologue.
The marine bioluminescent bacterium Photobacterium phosphoreum expresses a bifunctional methylenetetrahydrofolate dehydrogenase-cyclohydrolase with dual cofactor specificity. An investigation of the kinetic parameters of the P. phosphoreum enzyme indicate that its utilization of dinucleotide cofactors shares similarities with the human mitochondrial dehydrogenase-cyclohydrolase. Both enzymes exhibit dual cofactor specificity and the NAD(+)-dependent dehydrogenase activities from both enzymes can be activated by inorganic phosphate. Furthermore, an analysis of multiply aligned dehydrogenase-cyclohydrolase sequences from 11 species revealed that bacterial and mitochondrial enzymes are more closely related to each other than to the dehydrogenase-cyclohydrolase domains from eukaryotic trifunctional enzymes, and that the bacterial and mitochondrial enzymes share a common point of divergence. Since the NADP+ cofactor is kinetically favoured by a factor of 18 over NAD+, and is therefore likely to be the preferred in vivo cofactor, we propose that the P. phosphoreum enzyme and the human mitochondrial enzyme evolved from a common ancestral dehydrogenase-cyclohydrolase with dual cofactor specificity, but that cofactor preference in these two enzymes diverged in response to different metabolic requirements.
Pawelek
P D
PD
Department of Biochemistry, McGill University, Montréal, Québec, Canada.
MacKenzie
R E
RE
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004789:Enzyme Activation / Q000187:drug effects; D005816:Genetic Complementation Test; D006801:Humans; D007700:Kinetics; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism / Q000494:pharmacology; D010776:Photobacterium / Q000201:enzymology*; D010802:Phylogeny; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D009711:Nucleotides; D010710:Phosphates; D011994:Recombinant Proteins; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP)