Primary structure of human pancreatic elastase 2 determined by sequence analysis of the cloned mRNA
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), Vol. 26:23
- Country of Publication:
- United States
- Language:
- English
Similar Records
Human leukocyte and porcine pancreatic elastase: X-ray crystal structures, mechanism, substrate specificity, and mechanism-based inhibitors
Met-ase: Cloning and distinct chromosomal location of a serine protease preferentially expressed in human natural killer cells
Related Subjects
SERINE PROTEINASES
AMINO ACID SEQUENCE
DNA SEQUENCING
BIOCHEMISTRY
DNA-CLONING
ENZYMATIC HYDROLYSIS
LABELLED COMPOUNDS
MAN
MESSENGER-RNA
PANCREAS
RECOMBINANT DNA
ANIMALS
BODY
CHEMICAL REACTIONS
CHEMISTRY
CLONING
DECOMPOSITION
DIGESTIVE SYSTEM
DNA
ENDOCRINE GLANDS
ENZYMES
GLANDS
HYDROLASES
HYDROLYSIS
LYSIS
MAMMALS
MOLECULAR STRUCTURE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HYDROLASES
PRIMATES
RNA
SOLVOLYSIS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques