Cathepsin L1 - Revision history

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2019-08-19T21:52:46Z

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2019-07-31T20:10:01Z

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2019-07-31T20:09:42Z

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Wu3857: Created page with "{| align="left" | TOC |} {{#invoke:InfoboxforTarget|run|CTSL, CTSL1|[https://www.uniprot.org/uniprot/P07711 P07711]|Homo sapiens|Cys138|[http://pfam.xfam.org/family/PF..."

2019-07-31T20:08:11Z

Created page with "{| align="left" | __TOC__ |} {{#invoke:InfoboxforTarget|run|CTSL, CTSL1|[https://www.uniprot.org/uniprot/P07711 P07711]|Homo sapiens|Cys138|[http://pfam.xfam.org/family/PF..."

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{| align="left"
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{{#invoke:InfoboxforTarget|run|CTSL, CTSL1|[https://www.uniprot.org/uniprot/P07711 P07711]|Homo sapiens|Cys138|[http://pfam.xfam.org/family/PF00112 Peptidase C1 family]|[[:Category:Cathepsin L1|Ligand list]]|Protease}}
==Summary==

===Protein Function ===
Important for the overall degradation of proteins in lysosomes. (From Uniprot) 
Cathepsin L1 is a lysosomal cysteine protease that plays a major role in intracellular protein catabolism. Its substrates include collagen and elastin, as well as alpha-1 protease inhibitor, a major controlling element of neutrophil elastase activity. Cathepsin L1 has been implicated in several pathologic processes, including myofibril necrosis in myopathies and in myocardial ischemia, and in the renal tubular response to proteinuria. This protein, which is a member of the peptidase C1 family, is a dimer composed of disulfide-linked heavy and light chains, both produced from a single protein precursor. At least two transcript variants encoding the same protein have been found for this gene. CTSL1 has been shown to interact with Cystatin A. (From Wikipedia)
 

===Cys Function & Property===
Cys138 is one of the active sites of Cathepsin B, which is very close to His276 and Asn300 in space. These three residues formed a typical catalytic triad motif. 

* Hydrophobic property:
:[[File:511-hydro.png||600px]]
* SASA：
:Cys138: 11.897 A^2 

==Protein Sequence==

MNPTLILAAF CLGIASATLT FDHSLEAQWT KWKAMHNRLY GMNEEGWRRA 
VWEKNMKMIE LHNQEYREGK HSFTMAMNAF GDMTSEEFRQ VMNGFQNRKP 
RKGKVFQEPL FYEAPRSVDW REKGYVTPVK NQGQCGS'''C'''WA FSATGALEGQ 
MFRKTGRLIS LSEQNLVDCS GPQGNEGCNG GLMDYAFQYV QDNGGLDSEE 
SYPYEATEES CKYNPKYSVA NDTGFVDIPK QEKALMKAVA TVGPISVAID 
AGHESFLFYK EGIYFEPDCS SEDMDHGVLV VGYGFESTES DNNKYWLVKN 
SWGEEWGMGG YVKMAKDRRN HCGIASAASY PTV 


==Structural Information==
*Known structure with covalent ligand: 
:[https://www.rcsb.org/structure/3OF8 3OF8], [https://www.rcsb.org/structure/3OF9 3OF9], [https://www.rcsb.org/structure/2YJC 2YJC], [https://www.rcsb.org/structure/2XU1 2XU1], [https://www.rcsb.org/structure/2XU3 2XU3], [https://www.rcsb.org/structure/2YJB 2YJB] 
:[https://www.rcsb.org/structure/2YJ9 2YJ9], [https://www.rcsb.org/structure/2YJ8 2YJ8], [https://www.rcsb.org/structure/2YJ2 2YJ2], [https://www.rcsb.org/structure/2XU5 2XU5], [https://www.rcsb.org/structure/2XU4 2XU4], [https://www.rcsb.org/structure/3HWN 3HWN] 
:[https://www.rcsb.org/structure/3HHA 3HHA] 

*Protein structure:
::[[File:511.png|center|800px]]

==Related Pathway==
*[https://www.genome.jp/kegg-bin/show_pathway?ko04140 Autophagy - animal] 
*[https://www.genome.jp/kegg-bin/show_pathway?ko04142 Lysosome] 
*[https://www.genome.jp/kegg-bin/show_pathway?ko04145 Phagosome] 
*[https://www.genome.jp/kegg-bin/show_pathway?ko04210 Apoptosis] 
*[https://www.genome.jp/kegg-bin/show_pathway?ko04612 Antigen processing and presentation] 
*[https://www.genome.jp/kegg-bin/show_pathway?ko05205 Proteoglycans in cancer] 
*[https://www.genome.jp/kegg-bin/show_pathway?ko05323 Rheumatoid arthritis] 
*[https://www.genome.jp/kegg-bin/show_pathway?ko05418 Fluid shear stress and atherosclerosis] 

==Experimental Evidence==
:Crystallography, Homologous Analysis of Sequence, Enzymatic Assay

==Reference==
# Torkar A, Lenarčič B, Lah T, et al. '''Identification of new peptide amides as selective cathepsin L inhibitors: The first step towards selective irreversible inhibitors?[J].''' Bioorganic & medicinal chemistry letters, 2013, 23(10): 2968-2973. [https://www.ncbi.nlm.nih.gov/pubmed/?term=23562595 23562595] 
# 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] 
Falgueyret J P, Black W C, Cromlish W, et al. '''An activity-based probe for the determination of cysteine cathepsin protease activities in whole cells[J].''' Analytical biochemistry, 2004, 335(2): 218-227. [https://www.ncbi.nlm.nih.gov/pubmed/?term=15556560 15556560] 
# Shenoy, R. T. and J. Sivaraman (2011). "Structural basis for reversible and irreversible inhibition of human cathepsin L by their respective dipeptidyl glyoxal and diazomethylketone inhibitors." J Struct Biol 173(1): 14-19. [https://www.ncbi.nlm.nih.gov/pubmed/?term=20850545 20850545] 
# Hardegger L A, Kuhn B, Spinnler B, et al. '''Systematic investigation of halogen bonding in protein–ligand interactions[J].''' Angewandte Chemie International Edition, 2011, 50(1): 314-318. [https://www.ncbi.nlm.nih.gov/pubmed/?term=21184410 21184410] 
Hardegger L A, Kuhn B, Spinnler B, et al. '''Halogen bonding at the active sites of human cathepsin L and MEK1 kinase: efficient interactions in different environments[J].''' ChemMedChem, 2011, 6(11): 2048-2054. [https://www.ncbi.nlm.nih.gov/pubmed/?term=21898833 21898833] 
# Bethel P A, Gerhardt S, Jones E V, et al. '''Design of selective cathepsin inhibitors[J].''' Bioorganic & medicinal chemistry letters, 2009, 19(16): 4622-4625. [https://www.ncbi.nlm.nih.gov/pubmed/?term=19616430 19616430] 
# Asaad N, Bethel P A, Coulson M D, et al. '''Dipeptidyl nitrile inhibitors of Cathepsin L[J].''' Bioorganic & medicinal chemistry letters, 2009, 19(15): 4280-4283. [https://www.ncbi.nlm.nih.gov/pubmed/?term=19515558 19515558] 

[[Category:Targets|Targets]]
[[Category:Homo sapiens|Homo sapiens]]
[[Category:Protease|Protease]]
[[Category:Peptidase C1 family|Peptidase C1 family]]
[[Category:Autophagy - animal|Autophagy - animal]]
[[Category:Lysosome|Lysosome]]
[[Category:Phagosome|Phagosome]]
[[Category:Apoptosis|Apoptosis]]
[[Category:Antigen processing and presentation|Antigen processing and presentation]]
[[Category:Proteoglycans in cancer|Proteoglycans in cancer]]
[[Category:Fluid shear stress and atherosclerosis|Fluid shear stress and atherosclerosis]]
[[Category:Rheumatoid arthritis|Rheumatoid arthritis]]

@@ Line 61: / Line 61: @@
 # Asaad N, Bethel P A, Coulson M D, et al. '''Dipeptidyl nitrile inhibitors of Cathepsin L[J].''' Bioorganic & medicinal chemistry letters, 2009, 19(15): 4280-4283. [https://www.ncbi.nlm.nih.gov/pubmed/?term=19515558 19515558]<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:Autophagy - animal|Autophagy - animal]]
+[[Category:Autophagy - animal]]
-[[Category:Lysosome|Lysosome]]
+[[Category:Lysosome]]
-[[Category:Phagosome|Phagosome]]
+[[Category:Phagosome]]
-[[Category:Apoptosis|Apoptosis]]
+[[Category:Apoptosis]]
-[[Category:Antigen processing and presentation|Antigen processing and presentation]]
+[[Category:Antigen processing and presentation]]
-[[Category:Proteoglycans in cancer|Proteoglycans in cancer]]
+[[Category:Proteoglycans in cancer]]
-[[Category:Fluid shear stress and atherosclerosis|Fluid shear stress and atherosclerosis]]
+[[Category:Fluid shear stress and atherosclerosis]]
-[[Category:Rheumatoid arthritis|Rheumatoid arthritis]]
+[[Category:Rheumatoid arthritis]]

@@ Line 54: / Line 54: @@
 # Torkar A, Lenarčič B, Lah T, et al. '''Identification of new peptide amides as selective cathepsin L inhibitors: The first step towards selective irreversible inhibitors?[J].''' Bioorganic & medicinal chemistry letters, 2013, 23(10): 2968-2973. [https://www.ncbi.nlm.nih.gov/pubmed/?term=23562595 23562595]<br/>
 # Respondek T, Garner R N, Herroon M K, et al. '''Light activation of a cysteine protease inhibitor: caging of a peptidomimetic nitrile with Ru<sup>II</sup>(bpy)<sub>2</sub>[J].''' Journal of the American Chemical Society, 2011, 133(43): 17164-17167. [https://www.ncbi.nlm.nih.gov/pubmed/?term=21973207 21973207]<br/>
-Falgueyret J P, Black W C, Cromlish W, et al. '''An activity-based probe for the determination of cysteine cathepsin protease activities in whole cells[J].''' Analytical biochemistry, 2004, 335(2): 218-227. [https://www.ncbi.nlm.nih.gov/pubmed/?term=15556560 15556560]<br/>
+# Falgueyret J P, Black W C, Cromlish W, et al. '''An activity-based probe for the determination of cysteine cathepsin protease activities in whole cells[J].''' Analytical biochemistry, 2004, 335(2): 218-227. [https://www.ncbi.nlm.nih.gov/pubmed/?term=15556560 15556560]<br/>
 # Shenoy R T, Sivaraman J. '''Structural basis for reversible and irreversible inhibition of human cathepsin L by their respective dipeptidyl glyoxal and diazomethylketone inhibitors[J].''' Journal of structural biology, 2011, 173(1): 14-19. [https://www.ncbi.nlm.nih.gov/pubmed/?term=20850545 20850545]<br/>
 # Hardegger L A, Kuhn B, Spinnler B, et al. '''Systematic investigation of halogen bonding in protein–ligand interactions[J].''' Angewandte Chemie International Edition, 2011, 50(1): 314-318. [https://www.ncbi.nlm.nih.gov/pubmed/?term=21184410 21184410]<br/>
-Hardegger L A, Kuhn B, Spinnler B, et al. '''Halogen bonding at the active sites of human cathepsin L and MEK1 kinase: efficient interactions in different environments[J].''' ChemMedChem, 2011, 6(11): 2048-2054. [https://www.ncbi.nlm.nih.gov/pubmed/?term=21898833 21898833]<br/>
+# Hardegger L A, Kuhn B, Spinnler B, et al. '''Halogen bonding at the active sites of human cathepsin L and MEK1 kinase: efficient interactions in different environments[J].''' ChemMedChem, 2011, 6(11): 2048-2054. [https://www.ncbi.nlm.nih.gov/pubmed/?term=21898833 21898833]<br/>
 # Bethel P A, Gerhardt S, Jones E V, et al. '''Design of selective cathepsin inhibitors[J].''' Bioorganic & medicinal chemistry letters, 2009, 19(16): 4622-4625. [https://www.ncbi.nlm.nih.gov/pubmed/?term=19616430 19616430]<br/>
 # Asaad N, Bethel P A, Coulson M D, et al. '''Dipeptidyl nitrile inhibitors of Cathepsin L[J].''' Bioorganic & medicinal chemistry letters, 2009, 19(15): 4280-4283. [https://www.ncbi.nlm.nih.gov/pubmed/?term=19515558 19515558]<br/>

@@ Line 55: / Line 55: @@
 # Respondek T, Garner R N, Herroon M K, et al. '''Light activation of a cysteine protease inhibitor: caging of a peptidomimetic nitrile with Ru<sup>II</sup>(bpy)<sub>2</sub>[J].''' Journal of the American Chemical Society, 2011, 133(43): 17164-17167. [https://www.ncbi.nlm.nih.gov/pubmed/?term=21973207 21973207]<br/>
 Falgueyret J P, Black W C, Cromlish W, et al. '''An activity-based probe for the determination of cysteine cathepsin protease activities in whole cells[J].''' Analytical biochemistry, 2004, 335(2): 218-227. [https://www.ncbi.nlm.nih.gov/pubmed/?term=15556560 15556560]<br/>
-# Shenoy, R. T. and J. Sivaraman (2011). "Structural basis for reversible and irreversible inhibition of human cathepsin L by their respective dipeptidyl glyoxal and diazomethylketone inhibitors." J Struct Biol 173(1): 14-19. [https://www.ncbi.nlm.nih.gov/pubmed/?term=20850545 20850545]<br/>
+# Shenoy R T, Sivaraman J. '''Structural basis for reversible and irreversible inhibition of human cathepsin L by their respective dipeptidyl glyoxal and diazomethylketone inhibitors[J].''' Journal of structural biology, 2011, 173(1): 14-19. [https://www.ncbi.nlm.nih.gov/pubmed/?term=20850545 20850545]<br/>
 # Hardegger L A, Kuhn B, Spinnler B, et al. '''Systematic investigation of halogen bonding in protein–ligand interactions[J].''' Angewandte Chemie International Edition, 2011, 50(1): 314-318. [https://www.ncbi.nlm.nih.gov/pubmed/?term=21184410 21184410]<br/>
 Hardegger L A, Kuhn B, Spinnler B, et al. '''Halogen bonding at the active sites of human cathepsin L and MEK1 kinase: efficient interactions in different environments[J].''' ChemMedChem, 2011, 6(11): 2048-2054. [https://www.ncbi.nlm.nih.gov/pubmed/?term=21898833 21898833]<br/>

Cathepsin L1 - Revision history

Wu3857: /* Reference */

Wu3857: /* Reference */

Wu3857: /* Reference */

Wu3857: Created page with "{| align="left" | __TOC__ |} {{#invoke:InfoboxforTarget|run|CTSL, CTSL1|[https://www.uniprot.org/uniprot/P07711 P07711]|Homo sapiens|Cys138|[http://pfam.xfam.org/family/PF..."

Wu3857: Created page with "{| align="left" | TOC |} {{#invoke:InfoboxforTarget|run|CTSL, CTSL1|[https://www.uniprot.org/uniprot/P07711 P07711]|Homo sapiens|Cys138|[http://pfam.xfam.org/family/PF..."