Duodenases are a small subfamily of ruminant intestinal serine proteases that have undergone a remarkable diversification in cleavage specificity
| Autor: | Jukka Kervinen, Srinivas Akula, Jinhye Ryu, Michael Thorpe, Lars Hellman, Zhirong Fu, Chang Qiao, Gurdeep Chahal, Lawrence de Garavilla |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Swine Biochemistry law.invention Substrate Specificity 0302 clinical medicine Phage Display law Animal Cells Medicine and Health Sciences Mast Cells Phylogeny Connective Tissue Cells chemistry.chemical_classification Mammals Multidisciplinary biology Serine Endopeptidases Biochemistry and Molecular Biology Eukaryota Proteases Recombinant Proteins Enzymes Molecular Biology Display Techniques Connective Tissue Proteome Immunologi Vertebrates Recombinant DNA Medicine Anatomy Cellular Types Research Article Duodenum Science Immunology Lysozyme Tryptase Locus (genetics) Research and Analysis Methods 03 medical and health sciences Chymases Peptide Library Genetics Animals Amino Acid Sequence Molecular Biology Techniques Gene Molecular Biology Nutrition Molecular Biology Assays and Analysis Techniques Sheep Chymase Organisms Biology and Life Sciences Proteins Cell Biology Diet Gastrointestinal Tract 030104 developmental biology Enzyme Biological Tissue chemistry Genetic Loci Food Amniotes biology.protein Enzymology Cattle Zoology Digestive System Biokemi och molekylärbiologi 030215 immunology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 16, Iss 5, p e0252624 (2021) |
| ISSN: | 1932-6203 |
| Popis: | Ruminants have a very complex digestive system adapted for the digestion of cellulose rich food. Gene duplications have been central in the process of adapting their digestive system for this complex food source. One of the new loci involved in food digestion is the lysozyme c locus where cows have ten active such genes compared to a single gene in humans and where four of the bovine copies are expressed in the abomasum, the real stomach. The second locus that has become part of the ruminant digestive system is the chymase locus. The chymase locus encodes several of the major hematopoietic granule proteases. In ruminants, genes within the chymase locus have duplicated and some of them are expressed in the duodenum and are therefore called duodenases. To obtain information on their specificities and functions we produced six recombinant proteolytically active duodenases (three from cows, two from sheep and one from pigs). Two of the sheep duodenases were found to be highly specific tryptases and one of the bovine duodenases was a highly specific asp-ase. The remaining two bovine duodenases were dual enzymes with potent tryptase and chymase activities. In contrast, the pig enzyme was a chymase with no tryptase or asp-ase activity. These results point to a remarkable flexibility in both the primary and extended specificities within a single chromosomal locus that most likely has originated from one or a few genes by several rounds of local gene duplications. Interestingly, using the consensus cleavage site for the bovine asp-ase to screen the entire bovine proteome, it revealed Mucin-5B as one of the potential targets. Using the same strategy for one of the sheep tryptases, this enzyme was found to have potential cleavage sites in two chemokine receptors, CCR3 and 7, suggesting a role for this enzyme to suppress intestinal inflammation. |
| Databáze: | OpenAIRE |
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