Covalent Structure of a Group-Specific Protease from Rat Small Intestine~

Richard G. Woodbury*, Nobuhiko Katunuma, Keiko Kobayashi, Koiti Titani, Hans Neurath, Wayne F. Anderson, Brian W. Matthews, Richard G. Woodbur

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

“Group-specific” protease (GSP) is a serine protease, obtained from rat small intestine, which preferentially inactivates the apo forms of certain pyridoxal phosphate requiring enzymes. The enzyme contains 224 amino acid residues in a single polypeptide chain and three disulfide bonds. In the present work the covalent structure has been determined and its homologous relationship to those of chymotrypsin, trypsin, and elastase has been established (approximately 33% identity with each). The residues forming the “charge-relay” system of the active site of chymotrypsin (His-57, Asp-102, and Ser-195) are found in corresponding regions in GSP, whereas an alanyl residue at position 176 of GSP corresponds to a residue which participates in the primary substrate binding site in serine proteases (Asp-177 in trypsin; Ser-189 in chymotrypsin). Three disulfide bonds in GSP occur in similar positions in chymotrypsin, trypsin, and elastase. However, GSP lacks a disulfide bond which is present in all known serine proteases (linking Cys-191 to Cys-220 in chymotrypsin). In view of the close proximity of this bond to both the primary and the anti-parallel binding sites of various serine proteases, it is likely that its absence in GSP is related to the substrate specificity of this enzyme. It is concluded that GSP diverged from a common ancestor preceding chymotrypsin but following trypsin.

Original languageEnglish (US)
Pages (from-to)811-819
Number of pages9
JournalBiochemistry
Volume17
Issue number5
DOIs
StatePublished - Jan 1 1978

ASJC Scopus subject areas

  • Biochemistry

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