Protein splicing: estimation of the rate of O-N and S-N acyl rearrangements, the last step of the splicing process.
The last step in the sequence of reactions that lead to protein splicing is the intramolecular O-N or S-N acyl rearrangement of the ester or thioester linkage, respectively, between the two exteins and hydrolysis of the aminosuccinimide residue at the C-terminus of intein. This paper presents data on the rates of O-N and S-N acyl rearrangements of two model depsipeptides as a function of pH and temperature. The rates of rearrangement of both the oxygen ester and the thioester depsipeptide increased strikingly with pH, with the thioester being about 10(3) times more reactive at pH 5.5, and had a relatively low dependence on temperature, indicative of a low activating energy. The rates of O-N and S-N acyl rearrangement of these two model depsipeptides greatly exceed the rate of protein splicing, explaining why the last step of protein splicing can occur without catalysis by the intein.
Shao
Y
Y
Boston Biomedical Research Institute, Massachusetts, USA.
Paulus
H
H
D000215:Acylation; D002851:Chromatography, High Pressure Liquid; D004951:Esterification; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D019154:Protein Splicing; D013696:Temperature; D013816:Thermodynamics
D010455:Peptides