Cathepsin B
Cathepsin B is an enzymatic protein belonging to the peptidase (or protease) families. In humans, it is coded by the CTSB gene.[1][2]
Function
The protein encoded by this gene is a lysosomal cysteine protease composed of a dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. It is a member of the peptidase C1 family. At least five transcript variants encoding the same protein have been found for this gene.[3]
Clinical significance
Cathepsin B was once suspected as a candidate protease participating in the conversion of β-amyloid precursor protein into the amyloid plaques found in Alzheimer's disease patients. However, this function is now known to be mediated by BACE1 protease. It is now thought that cathepsin B can degrade β-amyloid precursor protein into harmless fragments. Thus, it is conceivable cathepsin B may play a pivotal role in the natural defense against Alzheimer's disease.[4] Overexpression of cathepsin B has been associated with esophageal adenocarcinoma and other tumors.[3]
Mutations in the CTSB gene have been linked to tropical pancreatitis, a form of chronic pancreatitis.[5]
Interactions
Cathepsin B has been shown to interact with cystatin B,[6][7] S100A10[8] and cystatin A.[6][9]
See also
References
- ^ Chan SJ, San Segundo B, McCormick MB, Steiner DF (October 1986). "Nucleotide and predicted amino acid sequences of cloned human and mouse preprocathepsin B cDNAs". Proc. Natl. Acad. Sci. U.S.A. 83 (20): 7721–5. doi:10.1073/pnas.83.20.7721. PMC 386793. PMID 3463996. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=386793.
- ^ Cao L, Taggart RT, Berquin IM, Moin K, Fong D, Sloane BF (February 1994). "Human gastric adenocarcinoma cathepsin B: isolation and sequencing of full-length cDNAs and polymorphisms of the gene". Gene 139 (2): 163–9. doi:10.1016/0378-1119(94)90750-1. PMID 8112600.
- ^ a b "Entrez Gene: CTSB cathepsin B". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1508.
- ^ Mueller-Steiner S, Zhou Y, Arai H, Roberson ED, Sun B, Chen J, Wang X, Yu G, Esposito L, Mucke L, Gan L (September 2006). "Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease". Neuron 51 (6): 703–14. doi:10.1016/j.neuron.2006.07.027. PMID 16982417. Lay summary – Science Blog.
- ^ Tandon RK (January 2007). "Tropical pancreatitis". J. Gastroenterol. 42 (Suppl 17): 141–7. doi:10.1007/s00535-006-1930-y. PMID 17238044.
- ^ a b Pavlova A, Björk I (September 2003). "Grafting of features of cystatins C or B into the N-terminal region or second binding loop of cystatin A (stefin A) substantially enhances inhibition of cysteine proteinases". Biochemistry 42 (38): 11326–33. doi:10.1021/bi030119v. PMID 14503883.
- ^ Pol E, Björk I (September 2001). "Role of the single cysteine residue, Cys 3, of human and bovine cystatin B (stefin B) in the inhibition of cysteine proteinases". Protein Sci. 10 (9): 1729–38. doi:10.1110/ps.11901. PMC 2253190. PMID 11514663. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2253190.
- ^ Mai J, Finley RL, Waisman DM, Sloane BF (April 2000). "Human procathepsin B interacts with the annexin II tetramer on the surface of tumor cells". J. Biol. Chem. 275 (17): 12806–12. doi:10.1074/jbc.275.17.12806. PMID 10777578.
- ^ Estrada S, Nycander M, Hill NJ, Craven CJ, Waltho JP, Björk I (May 1998). "The role of Gly-4 of human cystatin A (stefin A) in the binding of target proteinases. Characterization by kinetic and equilibrium methods of the interactions of cystatin A Gly-4 mutants with papain, cathepsin B, and cathepsin L". Biochemistry 37 (20): 7551–60. doi:10.1021/bi980026r. PMID 9585570.
Further reading
External links
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PDB gallery
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1csb: CRYSTAL STRUCTURE OF CATHEPSIN B INHIBITED WITH CA030 AT 2.1 ANGSTROMS RESOLUTION: A BASIS FOR THE DESIGN OF SPECIFIC EPOXYSUCCINYL INHIBITORS
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1gmy: CATHEPSIN B COMPLEXED WITH DIPEPTIDYL NITRILE INHIBITOR
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1huc: THE REFINED 2.15 ANGSTROMS X-RAY CRYSTAL STRUCTURE OF HUMAN LIVER CATHEPSIN B: THE STRUCTURAL BASIS FOR ITS SPECIFICITY
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1pbh: CRYSTAL STRUCTURE OF HUMAN RECOMBINANT PROCATHEPSIN B AT 3.2 ANGSTROM RESOLUTION
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1sp4: Crystal structure of NS-134 in complex with bovine cathepsin B: a two headed epoxysuccinyl inhibitor extends along the whole active site cleft
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2ipp: Crystal Structure of the tetragonal form of human liver cathepsin B
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2pbh: CRYSTAL STRUCTURE OF HUMAN PROCATHEPSIN B AT 3.3 ANGSTROM RESOLUTION
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3pbh: REFINED CRYSTAL STRUCTURE OF HUMAN PROCATHEPSIN B AT 2.5 ANGSTROM RESOLUTION
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| Caspase |
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| Fruit-derived |
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| Calpain |
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| Cathepsin |
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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