Primary structure of human pancreatic protease E determined by sequence analysis of the cloned mRNA

Journal Article · Tue Jun 16 04:00:00 EDT 1987 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00386a030· OSTI ID:6180638

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

Although protease E was isolated from human pancreas over 10 years ago, its amino acid sequence and relationship to the elastases have not been established. The authors report the isolation of a cDNA clone for human pancreatic protease E and determination of the nucleic acid sequence coding for the protein. The deduced amino acid sequence contains all of the features common to serine proteases. The substrate binding region is highly homologous to those of porcine and rat elastases 1, explaining the similar specificity for alanine reported for protease E and these elastases. However, the amino acid sequence outside the substrate binding region is less than 50% conserved, and there is a striking difference in the overall net charge for protease E (6-) and elastases 1 (8+). These findings confirm that protease E is a new member of the serine protease family. They have attempted to identify amino acid residues important for the interaction between elastases and elastin by examining the amino acid sequence differences between elastases and protease E. In addition to the large number of surface charge changes which are outside the substrate binding region, there are several changes which might be crucial for elastolysis: Leu-73/Arg-73; Arg-217A/Ala-217A; Arg-65A/Gln-65A; and the presence of two new cysteine residues (Cys-98 and Cys-99B) which computer modeling studies predict could form a new disulfide bond, not previously observed for serine proteases. They also present evidence which suggests that human pancreas does not synthesize a basic, alanine-specific elastase similar to porcine elastase 1.

• Research Organization: Veterans Administration Medical Center, Martinez, CA
• OSTI ID: 6180638
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:12; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACID SEQUENCE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DNA
DNA SEQUENCING
ENDOCRINE GLANDS
ENZYMES
EVEN-ODD NUCLEI
GLANDS
HYBRIDIZATION
HYDROLASES
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MESSENGER-RNA
MOLECULAR STRUCTURE
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PANCREAS
PEPTIDE HYDROLASES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RECOMBINANT DNA
RNA
SERINE PROTEINASES
STRUCTURAL CHEMICAL ANALYSIS
SULFUR 35
SULFUR ISOTOPES