Cathepsin K - Revision history

Wu3857: /* Reference */

2019-08-19T21:51:18Z

‎Reference

Wu3857 at 20:35, 29 July 2019

2019-07-29T20:35:42Z

Wu3857: /* Structural Information */

2019-07-29T02:15:07Z

‎Structural Information

Wu3857: Created page with "{| align="left" | TOC |} {{#invoke:InfoboxforTarget|run|Cat K, CTSK|[https://www.uniprot.org/uniprot/P43235 P43235]|Homo sapiens|Cys139|[http://pfam.xfam.org/family/PF..."

2019-07-29T02:06:56Z

Created page with "{| align="left" | __TOC__ |} {{#invoke:InfoboxforTarget|run|Cat K, CTSK|[https://www.uniprot.org/uniprot/P43235 P43235]|Homo sapiens|Cys139|[http://pfam.xfam.org/family/PF..."

New page

{| align="left"
| __TOC__
|}
{{#invoke:InfoboxforTarget|run|Cat K, CTSK|[https://www.uniprot.org/uniprot/P43235 P43235]|Homo sapiens|Cys139|[http://pfam.xfam.org/family/PF00112 Peptidase C1 family]|[[:Category:Cathepsin K|Ligand list]]}}
==Summary==

===Protein Function ===
Cathepsin K, abbreviated CTSK, is a member of the peptidase C1 protein family, is expressed predominantly in osteoclasts. Cathepsin K could catabolize elastin, collagen, and gelatin allow it to break down bone and cartilage. This catabolic activity is also partially responsible for the loss of lung elasticity and recoil in emphysema. Cathepsin K inhibitors, such as odanacatib, show great potential in the treatment of osteoporosis. Cathepsin K is degraded by Cathepsin S, called Controlled Cathepsin Cannibalism. 
Its expression is stimulated by inflammatory cytokines that are released after tissue injury. (From Wikipedia) 
Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation. (From Uniprot)
 

===Cys Function & Property===
Cys139 is one of the active sites of Cathepsin K, which is very close to His276 and Asn296 in space. These three residues formed a typical catalytic triad motif. 

* Hydrophobic property:
:[[File:492-hydro.png||600px]]
* SASA：
:Cys139: 11.382 A^2

==Protein Sequence==

MWGLKVLLLP VVSFALYPEE ILDTHWELWK KTHRKQYNNK VDEISRRLIW 
EKNLKYISIH NLEASLGVHT YELAMNHLGD MTSEEVVQKM TGLKVPLSHS 
RSNDTLYIPE WEGRAPDSVD YRKKGYVTPV KNQGQCGS'''C'''W AFSSVGALEG 
QLKKKTGKLL NLSPQNLVDC VSENDGCGGG YMTNAFQYVQ KNRGIDSEDA 
YPYVGQEESC MYNPTGKAAK CRGYREIPEG NEKALKRAVA RVGPVSVAID 
ASLTSFQFYS KGVYYDESCN SDNLNHAVLA VGYGIQKGNK HWIIKNSWGE 
NWGNKGYILM ARNKNNACGI ANLASFPKM 


==Structural Information==
*Known structures with covalent ligands: 
:[https://www.rcsb.org/structure/3H7D 3H7D], [https://www.rcsb.org/structure/3C9E 3C9E], [https://www.rcsb.org/structure/1ATK 1ATK], [https://www.rcsb.org/structure/1YT7 1YT7], [https://www.rcsb.org/structure/1Q6K 1Q6K] 
:[https://www.rcsb.org/structure/1U9V 1U9V], [https://www.rcsb.org/structure/1U9W 1U9W], [https://www.rcsb.org/structure/1U9X 1U9X], [https://www.rcsb.org/structure/1VSN 1VSN], [https://www.rcsb.org/structure/1YK7 1YK7] 
:[https://www.rcsb.org/structure/1YK8 1YK8], [https://www.rcsb.org/structure/2AUX 2AUX], [https://www.rcsb.org/structure/2AUZ 2AUZ], [https://www.rcsb.org/structure/3KW9 3KW9], [https://www.rcsb.org/structure/1AU0 1AU0] 
:[https://www.rcsb.org/structure/1AU2 1AU2], [https://www.rcsb.org/structure/1AU3 1AU3], [https://www.rcsb.org/structure/1AU4 1AU4], [https://www.rcsb.org/structure/1AYU 1AYU], [https://www.rcsb.org/structure/1AYW 1AYW] 
:[https://www.rcsb.org/structure/1NLJ 1NLJ], [https://www.rcsb.org/structure/1SNK 1SNK] 

*Protein structure:
[[File:492.png|center|800px]]

==Related Pathway==
*[https://www.genome.jp/kegg-bin/show_pathway?ko04142 Lysosome] 
*[https://www.genome.jp/kegg-bin/show_pathway?ko04210 Apoptosis] 
*[https://www.genome.jp/kegg-bin/show_pathway?ko04380 Osteoclast differentiation] 
*[https://www.genome.jp/kegg-bin/show_pathway?ko04620 Toll-like receptor signaling pathway] 
*[https://www.genome.jp/kegg-bin/show_pathway?ko05323 Rheumatoid arthritis] 

==Experimental Evidence==
:Crystallography

==Reference==
# Cherney M M, Lecaille F, Kienitz M, et al. '''Structure-activity analysis of cathepsin K/chondroitin 4-sulfate interactions[J].''' Journal of Biological Chemistry, 2011, 286(11): 8988-8998. [https://www.ncbi.nlm.nih.gov/pubmed/?term=21193413 21193413] 
# Li Z, Kienetz M, Cherney M M, et al. '''The crystal and molecular structures of a cathepsin K: chondroitin sulfate complex[J].''' Journal of molecular biology, 2008, 383(1): 78-91. [https://www.ncbi.nlm.nih.gov/pubmed/?term=18692071 18692071] 
# Zhao B, Janson C A, Amegadzie B Y, et al. '''Crystal structure of human osteoclast cathepsin K complex with E-64[J].''' Nature structural biology, 1997, 4(2): 109. [https://www.ncbi.nlm.nih.gov/pubmed/?term=9033588 9033588] 
# Respondek T, Garner R N, Herroon M K, et al. '''Light activation of a cysteine protease inhibitor: caging of a peptidomimetic nitrile with RuII(bpy)2[J].''' Journal of the American Chemical Society, 2011, 133(43): 17164-17167. [https://www.ncbi.nlm.nih.gov/pubmed/?term=21973207 21973207] 
# Barrett D G, Boncek V M, Catalano J G, et al. '''P2–P3 conformationally constrained ketoamide-based inhibitors of cathepsin K[J].''' Bioorganic & medicinal chemistry letters, 2005, 15(15): 3540-3546. [https://www.ncbi.nlm.nih.gov/pubmed/?term=15982880 15982880] 
# Catalano J G, Deaton D N, Furfine E S, et al. '''Exploration of the P1 SAR of aldehyde cathepsin K inhibitors[J].''' Bioorganic & medicinal chemistry letters, 2004, 14(1): 275-278. [https://www.ncbi.nlm.nih.gov/pubmed/?term=14684342 14684342] 
# Li C S, Deschenes D, Desmarais S, et al. '''Identification of a potent and selective non-basic cathepsin K inhibitor[J].''' Bioorganic & medicinal chemistry letters, 2006, 16(7): 1985-1989. [https://www.ncbi.nlm.nih.gov/pubmed/?term=16413777 16413777] 
# Deaton D N, Hassell A M, McFadyen R B, et al. '''Novel and potent cyclic cyanamide-based cathepsin K inhibitors[J].''' Bioorganic & medicinal chemistry letters, 2005, 15(7): 1815-1819. [https://www.ncbi.nlm.nih.gov/pubmed/?term=15780613 15780613] 
# Barrett D G, Deaton D N, Hassell A M, et al. '''Acyclic cyanamide-based inhibitors of cathepsin K[J].''' Bioorganic & medicinal chemistry letters, 2005, 15(12): 3039-3043. [https://www.ncbi.nlm.nih.gov/pubmed/?term=15896958 15896958] 
# Adkison K K, Barrett D G, Deaton D N, et al. '''Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors?[J].''' Bioorganic & medicinal chemistry letters, 2006, 16(4): 978-983. [https://www.ncbi.nlm.nih.gov/pubmed/?term=16290936 16290936] 
# Rankovic Z, Cai J, Kerr J, et al. '''Design and optimization of a series of novel 2-cyano-pyrimidines as cathepsin K inhibitors[J].''' Bioorganic & medicinal chemistry letters, 2010, 20(5): 1524-1527. [https://www.ncbi.nlm.nih.gov/pubmed/?term=20149657 20149657] 
# DesJarlais R L, Yamashita D S, Oh H J, et al. '''Use of X-ray co-crystal structures and molecular modeling to design potent and selective non-peptide inhibitors of cathepsin K[J].''' Journal of the American Chemical Society, 1998, 120(35): 9114-9115. DOI:10.1021/ja981171v
# Marquis R W, Yamashita D S, Ru Y, et al. '''Conformationally constrained 1, 3-diamino ketones: a series of potent inhibitors of the cysteine protease cathepsin K[J].''' Journal of medicinal chemistry, 1998, 41(19): 3563-3567. [https://www.ncbi.nlm.nih.gov/pubmed/?term=9733481 9733481] 
# Thompson S K, Halbert S M, Bossard M J, et al. '''Design of potent and selective human cathepsin K inhibitors that span the active site[J].''' Proceedings of the National Academy of Sciences, 1997, 94(26): 14249-14254. [https://www.ncbi.nlm.nih.gov/pubmed/?term=9405598 9405598] 
# Marquis R W, Ru Y, LoCastro S M, et al. '''Azepanone-based inhibitors of human and rat cathepsin K[J].''' Journal of medicinal chemistry, 2001, 44(9): 1380-1395. [https://www.ncbi.nlm.nih.gov/pubmed/?term=11311061 11311061] 
# Boros E E, Deaton D N, Hassell A M, et al. '''Exploration of the P2–P3 SAR of aldehyde cathepsin K inhibitors[J].''' Bioorganic & medicinal chemistry letters, 2004, 14(13): 3425-3429. [https://www.ncbi.nlm.nih.gov/pubmed/?term=15177446 15177446] 

[[Category:Targets|Targets]]
[[Category:Homo sapiens|Homo sapiens]]
[[Category:Peptidase C1 family|Peptidase C1 family]]
[[Category:Lysosome|Lysosome]]
[[Category:Apoptosis|Apoptosis]]
[[Category:Osteoclast differentiation|Osteoclast differentiation]]
[[Category:Toll-like receptor signaling pathway|Toll-like receptor signaling pathway]]
[[Category:Rheumatoid arthritis|Rheumatoid arthritis]]

@@ Line 68: / Line 68: @@
 # Boros E E, Deaton D N, Hassell A M, et al. '''Exploration of the P2–P3 SAR of aldehyde cathepsin K inhibitors[J].''' Bioorganic & medicinal chemistry letters, 2004, 14(13): 3425-3429. [https://www.ncbi.nlm.nih.gov/pubmed/?term=15177446 15177446]<br/>
-[[Category:Targets|Targets]]
+[[Category:Targets]]
-[[Category:Homo sapiens|Homo sapiens]]
+[[Category:Homo sapiens]]
-[[Category:Protease|Protease]]
+[[Category:Protease]]
-[[Category:Peptidase C1 family|Peptidase C1 family]]
+[[Category:Peptidase C1 family]]
-[[Category:Lysosome|Lysosome]]
+[[Category:Lysosome]]
-[[Category:Apoptosis|Apoptosis]]
+[[Category:Apoptosis]]
-[[Category:Osteoclast differentiation|Osteoclast differentiation]]
+[[Category:Osteoclast differentiation]]
-[[Category:Toll-like receptor signaling pathway|Toll-like receptor signaling pathway]]
+[[Category:Toll-like receptor signaling pathway]]
-[[Category:Rheumatoid arthritis|Rheumatoid arthritis]]
+[[Category:Rheumatoid arthritis]]

@@ Line 32: / Line 32: @@
 ==Structural Information==
 *Known structures with covalent ligands: <br/>
-:[https://www.rcsb.org/structure/3H7D 3H7D], [https://www.rcsb.org/structure/3C9E 3C9E], [https://www.rcsb.org/structure/1ATK 1ATK], [https://www.rcsb.org/structure/1YT7 1YT7], [https://www.rcsb.org/structure/1Q6K 1Q6K]<br/>
+:[https://www.rcsb.org/structure/3H7D 3H7D], [https://www.rcsb.org/structure/3C9E 3C9E], [https://www.rcsb.org/structure/1ATK 1ATK], [https://www.rcsb.org/structure/1YT7 1YT7], [https://www.rcsb.org/structure/1Q6K 1Q6K], [https://www.rcsb.org/structure/1SNK 1SNK]<br/>
-:[https://www.rcsb.org/structure/1U9V 1U9V], [https://www.rcsb.org/structure/1U9W 1U9W], [https://www.rcsb.org/structure/1U9X 1U9X], [https://www.rcsb.org/structure/1VSN 1VSN], [https://www.rcsb.org/structure/1YK7 1YK7]<br/>
+:[https://www.rcsb.org/structure/1U9V 1U9V], [https://www.rcsb.org/structure/1U9W 1U9W], [https://www.rcsb.org/structure/1U9X 1U9X], [https://www.rcsb.org/structure/1VSN 1VSN], [https://www.rcsb.org/structure/1YK7 1YK7], [https://www.rcsb.org/structure/1NLJ 1NLJ]<br/>
-:[https://www.rcsb.org/structure/1YK8 1YK8], [https://www.rcsb.org/structure/2AUX 2AUX], [https://www.rcsb.org/structure/2AUZ 2AUZ], [https://www.rcsb.org/structure/3KW9 3KW9], [https://www.rcsb.org/structure/1AU0 1AU0]<br/>
+:[https://www.rcsb.org/structure/1YK8 1YK8], [https://www.rcsb.org/structure/2AUX 2AUX], [https://www.rcsb.org/structure/2AUZ 2AUZ], [https://www.rcsb.org/structure/3KW9 3KW9], [https://www.rcsb.org/structure/1AU0 1AU0], [https://www.rcsb.org/structure/1AYW 1AYW]<br/>
-:[https://www.rcsb.org/structure/1AU2 1AU2], [https://www.rcsb.org/structure/1AU3 1AU3], [https://www.rcsb.org/structure/1AU4 1AU4], [https://www.rcsb.org/structure/1AYU 1AYU], [https://www.rcsb.org/structure/1AYW 1AYW]<br/>
+:[https://www.rcsb.org/structure/1AU2 1AU2], [https://www.rcsb.org/structure/1AU3 1AU3], [https://www.rcsb.org/structure/1AU4 1AU4], [https://www.rcsb.org/structure/1AYU 1AYU]<br/>
 *Protein structure:

@@ Line 2: / Line 2: @@
    | __TOC__
    |}
-{{#invoke:InfoboxforTarget|run|Cat K, CTSK|[https://www.uniprot.org/uniprot/P43235 P43235]|Homo sapiens|Cys139|[http://pfam.xfam.org/family/PF00112 Peptidase C1 family]|[[:Category:Cathepsin K|Ligand list]]}}
+{{#invoke:InfoboxforTarget|run|Cat K, CTSK|[https://www.uniprot.org/uniprot/P43235 P43235]|Homo sapiens|Cys139|[http://pfam.xfam.org/family/PF00112 Peptidase C1 family]|[[:Category:Cathepsin K|Ligand list]]|Protease}}
 ==Summary==
@@ Line 70: / Line 70: @@
 [[Category:Targets|Targets]]
 [[Category:Homo sapiens|Homo sapiens]]
 [[Category:Peptidase C1 family|Peptidase C1 family]]
 [[Category:Lysosome|Lysosome]]

Cathepsin K - Revision history

Wu3857: /* Reference */

Wu3857 at 20:35, 29 July 2019

Wu3857: /* Structural Information */

Wu3857: Created page with "{| align="left" | __TOC__ |} {{#invoke:InfoboxforTarget|run|Cat K, CTSK|[https://www.uniprot.org/uniprot/P43235 P43235]|Homo sapiens|Cys139|[http://pfam.xfam.org/family/PF..."

Wu3857: Created page with "{| align="left" | TOC |} {{#invoke:InfoboxforTarget|run|Cat K, CTSK|[https://www.uniprot.org/uniprot/P43235 P43235]|Homo sapiens|Cys139|[http://pfam.xfam.org/family/PF..."