Primary structure of human pancreatic elastase 2 determined by sequence analysis of the cloned mRNA

Journal Article · Tue Nov 17 04:00:00 EST 1987 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00397a010· OSTI ID:5303517

Fletcher, T S; Shen, W F; Largman, C

A cDNA encoding elastase 2 has been cloned from a human pancreatic cDNA library. The cDNA contains a translation initiation site and a poly(A) recognition site and encodes a protein of 269 amino acids, including a proposed 16-residue signal peptide. The amino acid sequence of the deduced mature protein contains a 12-residue activation peptide containing a cysteine at residue 1 similar to that of chymotryspin. The proposed active enzyme contains all of the characteristic active-site amino acids, including His-57, Asp-102, and Ser-195. The S1 binding pocket is bounded by Gly-216 and Ser-226, making this pocket intermediate in size between chymotrypsins and elastase 1 or protease E, consistent with the substrate specificity of elastase 2 for long-chain aliphatic or aromatic amino acids. Computer modeling studies using the amino acid sequence of elastase 2 superimposed on the X-ray structure of porcine elastase 1 suggest that a change of Gln-192 in elastase 1 to Asn-192 in elastase 2 may account for the lower catalytic efficiency of the latter enzyme. Several basic residues appear to be near the ends of the extended binding pocket of elastases which might serve to anchor the enzyme to the elastin substrate. These studies indicate that elastases 2 and elastase 1 both contain an Arg-65A as well as a basic dipeptide at 223/224 which is not present in chymotrypsins. In addition, Arg-217A is present in humaan elastase 2 but absent in rat pancreatic protein which has been proposed to be an elastase 2 on the basis of sequence homology, but which was not isolated during screening of rat pancreatic tissue extracts for elastolytic activity.

• Research Organization: Veterans Administration Medical Center, Martinez, CA
• OSTI ID: 5303517
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:23; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACID SEQUENCE
ANIMALS
BIOCHEMISTRY
BODY
CHEMICAL REACTIONS
CHEMISTRY
CLONING
DECOMPOSITION
DIGESTIVE SYSTEM
DNA
DNA SEQUENCING
DNA-CLONING
ENDOCRINE GLANDS
ENZYMATIC HYDROLYSIS
ENZYMES
GLANDS
HYDROLASES
HYDROLYSIS
LABELLED COMPOUNDS
LYSIS
MAMMALS
MAN
MESSENGER-RNA
MOLECULAR STRUCTURE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PANCREAS
PEPTIDE HYDROLASES
PRIMATES
RECOMBINANT DNA
RNA
SERINE PROTEINASES
SOLVOLYSIS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES