Cloning, expression, and characterization of a human 4'-phosphopantetheinyl transferase with broad substrate specificity.
A single candidate 4'-phosphopantetheine transferase, identified by BLAST searches of the human genome sequence data base, has been cloned, expressed, and characterized. The human enzyme, which is expressed mainly in the cytosolic compartment in a wide range of tissues, is a 329-residue, monomeric protein. The enzyme is capable of transferring the 4'-phosphopantetheine moiety of coenzyme A to a conserved serine residue in both the acyl carrier protein domain of the human cytosolic multifunctional fatty acid synthase and the acyl carrier protein associated independently with human mitochondria. The human 4'-phosphopantetheine transferase is also capable of phosphopantetheinylation of peptidyl carrier and acyl carrier proteins from prokaryotes. The same human protein also has recently been implicated in phosphopantetheinylation of the alpha-aminoadipate semialdehyde dehydrogenase involved in lysine catabolism (Praphanphoj, V., Sacksteder, K. A., Gould, S. J., Thomas, G. H., and Geraghty, M. T. (2001) Mol. Genet. Metab. 72, 336-342). Thus, in contrast to yeast, which utilizes separate 4'-phosphopantetheine transferases to service each of three different carrier protein substrates, humans appear to utilize a single, broad specificity enzyme for all posttranslational 4'-phosphopantetheinylation reactions.
Joshi
Anil K
AK
Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.
Zhang
Lei
L
Rangan
Vangipuram S
VS
Smith
Stuart
S
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002850:Chromatography, Gel; D003001:Cloning, Molecular; D003065:Coenzyme A / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D030541:Databases, Genetic; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D064429:Fatty Acid Synthases / Q000378:metabolism; D006801:Humans; D007313:Insecta; D007700:Kinetics; D008239:Lysine / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry; D013379:Substrate Specificity; D013997:Time Factors; D014018:Tissue Distribution; D017855:Transferases (Other Substituted Phosphate Groups) / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*
D017931:DNA Primers; D018076:DNA, Complementary; D012694:Serine; D064429:Fatty Acid Synthases; D017855:Transferases (Other Substituted Phosphate Groups); C021364:holo-(acyl-carrier-protein) synthase; D008239:Lysine; D003065:Coenzyme A