Enterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains
| Autor: | D. W. Mccourt, J E Sadler, Qingyu Wu, Y. Kitamoto, Xin Yuan |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Enteropeptidase
Proteases DNA Complementary medicine.medical_treatment Molecular Sequence Data Biology Structure-Activity Relationship medicine Animals Humans Amino Acid Sequence Cloning Molecular Trypsinogen activation Protein precursor Peptide sequence chemistry.chemical_classification Binding Sites Multidisciplinary Protease Base Sequence Sequence Homology Amino Acid Membrane Proteins Trypsin Amino acid Intestines chemistry Biochemistry Cattle Digestion Sequence Analysis Research Article medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 91:7588-7592 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Enterokinase is a protease of the intestinal brush border that specifically cleaves the acidic propeptide from trypsinogen to yield active trypsin. This cleavage initiates a cascade of proteolytic reactions leading to the activation of many pancreatic zymogens. The full-length cDNA sequence for bovine enterokinase and partial cDNA sequence for human enterokinase were determined. The deduced amino acid sequences indicate that active two-chain enterokinase is derived from a single-chain precursor. Membrane association may be mediated by a potential signal-anchor sequence near the amino terminus. The amino terminus of bovine enterokinase also meets the known sequence requirements for protein N-myristoylation. The amino-terminal heavy chain contains domains that are homologous to segments of the low density lipoprotein receptor, complement components C1r and C1s, the macrophage scavenger receptor, and a recently described motif shared by the metalloprotease meprin and the Xenopus A5 neuronal recognition protein. The carboxyl-terminal light chain is homologous to the trypsin-like serine proteases. Thus, enterokinase is a mosaic protein with a complex evolutionary history. The amino acid sequence surrounding the amino terminus of the enterokinase light chain is ITPK-IVGG (human) or VSPK-IVGG (bovine), suggesting that single-chain enterokinase is activated by an unidentified trypsin-like protease that cleaves the indicated Lys-Ile bond. Therefore, enterokinase may not be the "first" enzyme of the intestinal digestive hydrolase cascade. The specificity of enterokinase for the DDDDK-I sequence of trypsinogen may be explained by complementary basic-amino acid residues clustered in potential S2-S5 subsites. |
| Databáze: | OpenAIRE |
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