Metal-ion-assisted hydrolysis of dipeptides involving a serine residue in a neutral aqueous solutionElectronic supplementary information (ESI) available: Kinetic studies involving pH and concentration profiles of the rate constant. See http://www.rsc.org/suppdata/ob/b2/b209565c/

Abstract

Dipeptides having a serine residue at the C-terminus, X-Ser, where X is an appropriate amino acid residue, were efficiently hydrolyzed in the presence of ZnCl2 at pH 7.0. The rapid hydrolysis of X-Ser is due to an autocatalysis of the hydroxy group in the serine residue, and is found to be accelerated by a metal ion, in particular by ZnCl2. Roles of the metal ion in the hydrolysis of peptides involving a serine residue, in relation to the recently reported protein cleavages, are discussed.

Spontaneous cleavage of proteins at serine and threonine is facilitated by zinc

“…In these cases, co‐ordination to an alpha amino group is not possible, but other amino acid chelators in particular the side chain of His can act in a comparable manner. Based on the dipeptide data (Yashiro et al ., 2003), it is very likely that other divalent metals such as Ni, Ca, Cd and Mg can also accelerate autolysis adjacent to Ser residues in long‐lived proteins; however, this was not investigated in this study. To characterize the mechanism of cleavage, a number of factors were considered.…”

“…As dipeptide cleavage had been reported to be catalysed by divalent metals, in particular zinc (Yashiro et al ., 2003), zinc was incorporated in the current study. As shown in Fig.…”

“…Our work extends a publication on dipeptides by Yahiro et al . (Yashiro et al ., 2003) where they observed cleavage adjacent to Ser was assisted by a number of divalent metal ions, in particular, zinc. Their proposed mechanism involved coordination of the metals to the free alpha amino group of the dipeptide, as well as to the carbonyl group of the peptide bond on the N‐terminal side of the Ser residue.…”

Metal assisted peptide bond hydrolysis: Chemistry, biotechnology and toxicological implications

“…Yashiro and co-workers studied the ability of the number of metal chlorides to cleave dipeptides [18]. Incubation of peptides with almost all metal ions tested significantly increased the amount of hydrolysis products.…”

“…Conversion degrees comparable to Gly-Ser or even higher were observed for Phe-Ser (91%), Leu-Ser (81%), and Pro-Ser (80%) after 24 h, at pH 7.0 and 70 • C for Zn(II)-assisted hydrolysis. The decrease in temperature by 20 • C resulted in an almost four-fold reduction of the yield of Zn(II)-assisted Gly-Ser hydrolysis [18].…”