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In biology and biochemistry, protease inhibitors, or antiproteases, are molecules that inhibit the function of proteases. Many naturally occurring protease inhibitors are proteins.
Cathepsins are proteases found in all animals as well as other organisms. There are approximately a dozen members of this family, which are distinguished by their structure, catalytic mechanism, and which proteins they cleave. Most of the members become activated at the low pH found in lysosomes. Thus, the activity of this family lies almost entirely within those organelles. There are, however, exceptions such as cathepsin K, which works extracellularly after secretion by osteoclasts in bone resorption. Cathepsins have a vital role in mammalian cellular turnover.
Cathepsin S is a protein that in humans is encoded by the CTSS gene. Transcript variants utilizing alternative polyadenylation signals exist for this gene.
Cathepsin O is an enzyme that in humans is encoded by the CTSO gene.
The cystatins are a family of cysteine protease inhibitors which share a sequence homology and a common tertiary structure of an alpha helix lying on top of an anti-parallel beta sheet. The family is subdivided as described below.
Cathepsin G is a protein that in humans is encoded by the CTSG gene. It is one of the three serine proteases of the chymotrypsin family that are stored in the azurophil granules, and also a member of the peptidase S1 protein family. Cathepsin G plays an important role in eliminating intracellular pathogens and breaking down tissues at inflammatory sites, as well as in anti-inflammatory response.
Cathepsin B belongs to a family of lysosomal cysteine proteases and plays an important role in intracellular proteolysis. In humans, cathepsin B is encoded by the CTSB gene. Cathepsin B is upregulated in certain cancers, in pre-malignant lesions, and in various other pathological conditions.
Cathepsin D is a protein that in humans is encoded by the CTSD gene. This gene encodes a lysosomal aspartyl protease composed of a protein dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. Cathepsin D is an aspartic endo-protease that is ubiquitously distributed in lysosomes. The main function of cathepsin D is to degrade proteins and activate precursors of bioactive proteins in pre-lysosomal compartments. This proteinase, which is a member of the peptidase A1 family, has a specificity similar to but narrower than that of pepsin A. Transcription of the CTSD gene is initiated from several sites, including one that is a start site for an estrogen-regulated transcript. Mutations in this gene are involved in the pathogenesis of several diseases, including breast cancer and possibly Alzheimer disease. Homozygous deletion of the CTSD gene leads to early lethality in the postnatal phase. Deficiency of CTSD gene has been reported an underlying cause of neuronal ceroid lipofuscinosis (NCL).
Cathepsin L1 is a protein that in humans is encoded by the CTSL1 gene.
Granulin is a protein that in humans is encoded by the GRN gene. Each granulin protein is cleaved from the precursor progranulin, a 593 amino acid long and 68.5 kDa protein. While the function of progranulin and granulin have yet to be determined, both forms of the protein have been implicated in development, inflammation, cell proliferation and protein homeostasis. The 2006 discovery of the GRN mutation in a population of patients with frontotemporal dementia has spurred much research in uncovering the function and involvement in disease of progranulin in the body. While there is a growing body of research on progranulin's role in the body, studies on specific granulin residues are still limited.
Cystatin-A is a protein that in humans is encoded by the CSTA gene.
Cystatin-B is a protein that in humans is encoded by the CSTB gene.
Cathepsin H is a protein that in humans is encoded by the CTSH gene.
Transmembrane protease, serine 2 is an enzyme that in humans is encoded by the TMPRSS2 gene.
Cathepsin Z, also called cathepsin X or cathepsin P, is a protein that in humans is encoded by the CTSZ gene. It is a member of the cysteine cathepsin protease family, which has 11 members. As one of the 11 cathepsins, cathepsin Z contains distinctive features from others. Cathepsin Z has been reported involved in cancer malignancy and inflammation.
Cathepsin L2, also known as cathepsin V and encoded by the CTSV gene, is a human gene.
Cathepsin W is a protein that in humans is encoded by the CTSW gene.
Serpin B13 is a protein that in humans is encoded by the SERPINB13 gene.
Cathepsin F is a protein that in humans is encoded by the CTSF gene.
E-64 is an epoxide which can irreversibly inhibit a wide range of cysteine peptidases.
References
- ↑ Barrett AJ, Kirschke H (1981). "Cathepsin B, Cathepsin H, and cathepsin L". Methods in Enzymology. 80 Pt C: 535–561. doi:10.1016/s0076-6879(81)80043-2. PMID 7043200.
- ↑ Barrett AJ, Buttle DJ, Mason RW (1988). "Lysosomal cysteine proteinases". ISI Atlas of Science. Biochemistry. 1: 256–260.
- ↑ Joseph LJ, Chang LC, Stamenkovich D, Sukhatme VP (May 1988). "Complete nucleotide and deduced amino acid sequences of human and murine preprocathepsin L. An abundant transcript induced by transformation of fibroblasts". The Journal of Clinical Investigation. 81 (5): 1621–1629. doi:10.1172/JCI113497. PMC 442598 . PMID 2835398.
- ↑ Kirschke H, Wikstrom P, Shaw E (February 1988). "Active center differences between cathepsins L and B: the S1 binding region". FEBS Letters. 228 (1): 128–130. doi: 10.1016/0014-5793(88)80600-8 . PMID 3342870.
- ↑ Dickinson DP (2002). "Cysteine Peptidases of Mammals: Their Biological Roles and Potential Effects in the Oral Cavity and Other Tissues in Health and Disease". Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists. 13 (3): 238–75. doi:10.1177/154411130201300304. PMID 12090464.
- 1 2 Jackson CB, Farzan M, Chen B, Choe H (January 2022). "Mechanisms of SARS-CoV-2 entry into cells". Nature Reviews. Molecular Cell Biology. 23 (1): 3–20. doi:10.1038/s41580-021-00418-x. PMC 8491763 . PMID 34611326.
- ↑ Gomes CP, Fernandes DE, Casimiro F, da Mata GF, Passos MT, Varela P, et al. (2022). "Cathepsin L in COVID-19: From Pharmacological Evidences to Genetics". Frontiers in Cellular and Infection Microbiology. 10: 589505. doi:10.3389/fcimb.2020.589505. PMC 7753008 . PMID 33364201.
- ↑ Berdowska I, Matusiewicz M (October 2021). "Cathepsin L, transmembrane peptidase/serine subfamily member 2/4, and other host proteases in COVID-19 pathogenesis - with impact on gastrointestinal tract". World Journal of Gastroenterology. 27 (39): 6590–6600. doi:10.3748/wjg.v27.i39.6590. PMC 8554394 . PMID 34754154.
- ↑ Venkatesh K, Prasanth B, Rajesh P, Annie JG, Mukesh P, Jesu A (2014). "A murrel cysteine protease, cathepsin L: bioinformatics characterization, gene expression and proteolytic activity". Biologia. 39: 395–406. doi: 10.2478/s11756-013-0326-8 .
- ↑ Sevenich L, Pennacchio LA, Peters C, Reinheckel T (July 2006). "Human cathepsin L rescues the neurodegeneration and lethality in cathepsin B/L double-deficient mice". Biological Chemistry. 387 (7): 885–91. doi:10.1515/BC.2006.112. PMID 16913838.
