title: Evolutionary relationships of the prolyl oligopeptidase family enzymes.
abstract: The prolyl oligopeptidase (POP) family of serine proteases includes prolyl oligopeptidase, dipeptidyl peptidase IV, acylaminoacyl peptidase and oligopeptidase B. The enzymes of this family specifically hydrolyze oligopeptides with less than 30 amino acids. Many of the POP family enzymes have evoked pharmaceutical interest as they have roles in the regulation of peptide hormones and are involved in a variety of diseases such as dementia, trypanosomiasis and type 2 diabetes. In this study we have clarified the evolutionary relationships of these four POP family enzymes and analyzed POP sequences from different sources. The phylogenetic trees indicate that the four enzymes were present in the last common ancestor of all life forms and that the beta-propeller domain has been part of the family for billions of years. There are striking differences in the mutation rates between the enzymes and POP was found to be the most conserved enzyme of this family. However, the localization of this enzyme has changed throughout evolution, as three archaeal POPs seem to be membrane bound and one third of the bacterial as well as two eukaryotic POPs were found to be secreted out of the cell. There are also considerable distinctions between the mutation rates of the different substrate binding subsites of POP. This information may help in the development of species-specific POP inhibitors.
authors.affiliation: Department of Pharmacology and Toxicology, University of Kuopio, Finland. Jarkko.Venalainen@uku.fi
authors.forename: Jarkko I
authors.initials: JI
authors.lastname: Venäläinen
authors.forename: Risto O
authors.initials: RO
authors.lastname: Juvonen
authors.forename: Pekka T
authors.initials: PT
authors.lastname: Männistö
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D000085822:Prolyl Oligopeptidases; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases