title: Glutaminyl cyclases from animals and plants: a case of functionally convergent protein evolution.
abstract: Several mammalian peptide hormones and proteins from plant and animal origin contain an N-terminal pyroglutamic acid (pGlu) residue. Frequently, the moiety is important in exerting biological function in either mediating interaction with receptors or stabilizing against N-terminal degradation. Glutaminyl cyclases (QCs) were isolated from different plants and animals catalyzing pGlu formation. The recent resolution of the 3D structures of Carica papaya and human QCs clearly supports different evolutionary origins of the proteins, which is also reflected by different enzymatic mechanisms. The broad substrate specificity is revealed by the heterogeneity of physiological substrates of plant and animal QCs, including cytokines, matrix proteins and pathogenesis-related proteins. Moreover, recent evidence also suggests human QC as a catalyst of pGlu formation at the N-terminus of amyloid peptides, which contribute to Alzheimer's disease. Obviously, owing to its biophysical properties, the function of pGlu in plant and animal proteins is very similar in terms of stabilizing or mediating protein and peptide structure. It is possible that the requirement for catalysis of pGlu formation under physiological conditions may have triggered separate evolution of QCs in plants and animals.
authors.affiliation: Probiodrug AG, Biocenter, Weinbergweg 22, D-06120 Halle/Saale, Germany. stephan.schilling@probiodrug.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Schilling
authors.forename: Claus
authors.initials: C
authors.lastname: Wasternack
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Demuth
mesh_terms: D019881:Aminoacyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002384:Catalysis; D019143:Evolution, Molecular; D006801:Humans; D010944:Plants / Q000201:enzymology* / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D019881:Aminoacyltransferases; C059280:glutaminyl-peptide cyclotransferase