Pancreatic elastase

Pancreatic elastase is a form of elastase that is produced in the acinar cells of the pancreas, initially produced as an inactive zymogen and later activated in the duodenum by trypsin. Elastases form a subfamily of serine proteases, characterized by a distinctive structure consisting of two beta barrel domains converging at the active site that hydrolyze amides and esters amongst many proteins in addition to elastin, a type of connective tissue that holds organs together. Pancreatic elastase 1 is a serine endopeptidase, a specific type of protease that has the amino acid serine at its active site. Although the recommended name is pancreatic elastase, it can also be referred to as elastase 1, pancreatopeptidase, PE, or serine elastase. The first isozyme, pancreatic elastase 1, was initially thought to be expressed in the pancreas. However it was later discovered that it was the only chymotrypsin like elastase that was not expressed in the pancreas. In fact, pancreatic elastase is expressed in basal layers of epidermis (at protein level). Hence pancreatic elastase 1 has been renamed elastase 1 (ELA1) or chymotrypsin like elastase family, member 1 (CELA1). However it was later discovered that it was expressed in skin keratinocytes. Clinical literature that describes human elastase 1 activity in the pancreas or fecal material is actually referring to chymotrypsin like elastase family, member 3B (CELA3B).

Pancreatic elastase is a compact globular protein with a hydrophobic core. This enzyme is formed by three subunits. Each subunit binds one calcium ion (cofactor). There are three important metal binding sites in amino acids 77, 82, 87. The catalytic triad , located in the active site is formed by three hydrogen bonded amino acid residues (H71, D119, S214), and plays an essential role in the cleaving ability of all proteases. It is composed of a single peptide chain of 240 amino acids and contains 4 disulfide bridges. It has a high degree of sequence identity with pancreatic elastases that correspond to other species, such as the rat's, with whom it shares 86% of its sequence. Its enzymatic activity is a result of the specific three dimensional conformation which its single polypeptide chain adopts, and therefore, activity is lost by denaturation and/or conformational changes.

Mutations of the CELA1 gene were suspected to be associated with diffuse nonepidermolytic palmoplantar keratoderma (diffuse NEPPK). A possible polymorphism of the CELA1 gene coding this protein was found. On a secondary structure level, this polymorphism manifests itself in an excision of a short sequence of CELA1. The disappeared sequence carries the key amino acid residues Val 227 and Thr 239, which contribute to the substrate specificity of elastase I (highlighted in Figure 3), as well as five of the eight amino acids involved in the primary contact of the elafin(inhibitor)/elastase complex formation. These observations imply that the sequence variant might modify the substrate specificity of the enzyme and abolish the inhibitor binding capability. Though there were no obvious pathogenic epidermal abnormalities associated with the truncated ELA1 variant, it is possible that carriers of the polymorphism may be at greater risk of developing the common skin diseases such as psoriasis and eczema (genetic and histologic studies will be required to investigate the role of ELA1 in these common epidermal disorders.). This process results in the removal of an activation peptide from the N terminal, that enables the enzyme to adopt its native conformation.

Glycosylation at Asn79 and Asn233.