Cathepsin k
From Proteopedia
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<Structure load='1atk' size='350' frame='true' align='right' caption='Human Cathepsin K' scene='72/727885/Cathepsin_k_helix_sheet/1' /> | <Structure load='1atk' size='350' frame='true' align='right' caption='Human Cathepsin K' scene='72/727885/Cathepsin_k_helix_sheet/1' /> | ||
| - | <scene name='72/727885/Cathepsin_k_helix_sheet/1'>Cathepsin K</scene> is initially synthesized in its inactive form, pre-procathepsin k, a 37-kDa protein made up of a single peptide chain 329 amino acids in length <ref name="mcq">doi:10.1074/jbc.272.21.13955</ref><ref name=" | + | <scene name='72/727885/Cathepsin_k_helix_sheet/1'>Cathepsin K</scene> is initially synthesized in its inactive form, pre-procathepsin k, a 37-kDa protein made up of a single peptide chain 329 amino acids in length <ref name="mcq">doi:10.1074/jbc.272.21.13955</ref><ref name="boss">doi:10.1074/jbc.271.21.12517</ref>. The pre-procathepsin k sequence has three distinct features: a signal peptide, consisting of the first 15 amino acids at the N-terminus; a propeptide, comprising amino acids 16-114; and the main chain, which makes up the final 215 amino acids ending at the C-Terminus (9,10). When the enzyme is activated, the signal peptide and propeptide portions are cleaved to produce the mature Cathepsin K protein weighing 27-kDa <ref name="mcq"/><ref name="boss"/>. |
| - | The <scene name='72/727885/Cathepsin_k_active_site/1'>active site</scene> of Cathepsin K consists of three residues: CYS25, HIS162, and ASN182 | + | The <scene name='72/727885/Cathepsin_k_active_site/1'>active site</scene> of Cathepsin K consists of three residues: CYS25, HIS162, and ASN182 <ref name="zao">doi:10.1038/nsb0297-109</ref>. |
Revision as of 00:03, 1 April 2016
Contents |
Structure
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is initially synthesized in its inactive form, pre-procathepsin k, a 37-kDa protein made up of a single peptide chain 329 amino acids in length [1][2]. The pre-procathepsin k sequence has three distinct features: a signal peptide, consisting of the first 15 amino acids at the N-terminus; a propeptide, comprising amino acids 16-114; and the main chain, which makes up the final 215 amino acids ending at the C-Terminus (9,10). When the enzyme is activated, the signal peptide and propeptide portions are cleaved to produce the mature Cathepsin K protein weighing 27-kDa [1][2].
The of Cathepsin K consists of three residues: CYS25, HIS162, and ASN182 [3].
Function
Cathepsin K is the most abundant cysteine protease produced by osteoclasts, the multinuclear cells responsible for bone resorption (6,7). Osteoclasts implement bone resorption by secreting acid onto the bone surface which demineralizes bone tissue, followed by proteases – including cathepsins – which degrade the bone matrix (6,8). Cathepsin K can cleave type I and type II collagen, major components of bone and cartilage matrices (4,5). This enzyme is unique among other cysteine proteases in that it can cleave collagen at multiple sites and in its triple helix (2).
Disease
Deficiencies in Cathepsin K have been shown to cause pycnodysostosis, caused by reduced bone resorption and characterized by increased bone density and short stature (3). Cathepsin K inhibitors have been thus thought potential treatments for diseases involving excessive bone or cartilage resorption, such as osteoporosis and autoimmue arthritis (1,4,6). However, as demineralization of bone can continue without Cathepsin k, the inhibition of Cathespin K may merely result in the accumulation of weakened bone tissue (7).
Relevance
</StructureSection>
References
- ↑ 1.0 1.1 doi: https://dx.doi.org/10.1074/jbc.272.21.13955
- ↑ 2.0 2.1 doi: https://dx.doi.org/10.1074/jbc.271.21.12517
- ↑ doi: https://dx.doi.org/10.1038/nsb0297-109
