Written by Aileen Sheehy
Proteolytic enzymes or ‘peptidases’ are extremely important for all living species. They are responsible for the natural breakdown of all proteins and control the activity of almost half of all proteins. Without peptidases there could be no life. Prior to this study there had only been six identified classes of peptidase: serine, cysteine, threonine, aspartic, glutamic or metallo catalytic type.
Peptidases work by catalysing the breaking of chemical bonds between amino acids; the building blocks of proteins. They generally work by a process called hydrolysis. This is where a water molecule attacks and breaks a specific chemical bond. These peptidases accelerate that breakage.
A team from the Wellcome Trust Sanger Institute have identified a seventh (doi:10.1074/jbc.M111.260026), unusual proteolytic enzyme in an asparagine catalytic type. This is only one of three proteolytic catalytic types to be discovered in over 50 years, the last discovered in 2004. This study has been picked as one of 20 best papers published by the Journal of Biological Chemistry in 2011, out of a total of 4,000 papers.
The inclusion of asparagine peptidases is debatable as this catalytic type does not behave like other peptidases. It does not use hydrolysis to achieve bond breakage. Asparagine forms a cyclic chemical structure that can then attack and break a chemical bond in proteins under the right circumstances. This is an alternative method to hydrolysis for protein degradation.
“As peptidases cleave these bonds using hydrolysis and this new catalytic type doesn’t, it was difficult to actually identify what kind of enzyme family this would fall under,” says Dr Alex Bateman, joint author from the Wellcome Trust Sanger Institute. “After much time searching through many digital libraries, we finally came to the conclusion that this enzyme fitted the profile of lyase.”
Lyases are enzymes that catalyse the breaking of chemical bonds without using the processes of hydrolysis or oxidation, a reaction where a chemical molecule loses one or more electrons
“To my knowledge, not only is this the first time we’ve found that a lyase can be used to break a chemical bond in a protein, this is the first time we’ve seen the breakdown of proteins by a process that does not include hydrolysis,” explains Dr Neil Rawlings, joint author from the Wellcome Trust Sanger Institute. “Proteolytic enzymes play a fundamental part of life. This type of discovery does not come along very often and may not come again.
“It is a great surprise and a tremendous honour to have our research recognised by the Journal of Biological Chemistry.”
Neil David Rawlings, Alan John Barrett, Alex Bateman. (2011) ‘Asparagine Peptide Lyases: A SEVENTH CATALYTIC TYPE OF PROTEOLYTIC ENZYMES’