Sequence and structure of the rat housekeeping PBG-D isoform.

ABSTRACT

Porphobilinogen deaminase (PBG-D), a key enzyme in the tetrapyrrole biosynthetic pathway, is encoded by a single gene containing two different promoters. The upstream promoter, found in all cell types, initiates the transcription of the housekeeping PBG-D isoform, whereas the downstream one is erythroid-specific. In this study, we provide the first full sequence of a 1086bp cDNA covering the coding region for the rat ubiquitous PBG-D and its primary amino acid sequence. The cDNA encodes a 39,361 Da protein composed of 361 amino acids. Nucleotide sequence comparison between both isoforms from rat shows similarities of 99.5%, with four changes (C/G) in exon 8 and only one (C/A) in exon 12. Secondary structure prediction reveals that 76.5% of the amino acids from exon 1 are located in a loop. Potential phosphorylation, glycosylation, and myristoylation sites were revealed through motif searches. Housekeeping PBG-D contains coiled-coil segments known to be involved in dynamic rearrangements in the active site.