We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

Cathepsin

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:04, 19 January 2025) (edit) (undo)
 
(61 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1pbh.png|left|200px|thumb|Crystal structure of wild-type human procathepsin B, [[1pbh]]]]
+
<StructureSection load='' size='350' side='right' scene='42/421669/Cv/10' caption='human cathepsin B complex with inhibitor [[3ai8]]'>
-
{{STRUCTURE_1pbh| PDB=1pbh | SIZE=300| SCENE=Cathepsin/Cv/1 |right|CAPTION=human procathepsin B, [[1pbh]] }}
+
== Function ==
-
[[Cathepsin]] (CTS) is a protease which becomes activated at low pH. It is found in lysosomes. Members of the CTS group are denoted as CTSA, CTSB etc and cleave proteins at different peptide bonds. The CTSs are expressed as an inactive precursor pro-CTS (PCTS) which become active when a long residue prosegment is cleaved off producing the mature CTS (MCTS). The images at the left and at the right correspond to one representative Cathepsin, ''i.e.'' the crystal structure of wild-type human procathepsin B ([[1pbh]]).
+
[[Cathepsin]] (CTS) is a protease which becomes activated at low pH. It is found in lysosomes. Members of the CTS group are denoted as CTSA, CTSB etc and cleave proteins at different peptide bonds. The CTSs are expressed as an inactive precursor '''pro-CTS''' (PCTS) which becomes active when a long residue prosegment is cleaved off producing the mature CTS (MCTS).<ref>PMID:15751268</ref> For details on pro-CTS see [[Molecular Playground/Human PPCA]].
-
{{TOC limit|limit=2}}
+
*'''CTS B, F, H, L, L1, L2 or V''' are cysteine proteases.<br />
-
<br />
+
*'''CTS D, E''' are aspartyl proteases which degrade insulin.<br />
-
<br />
+
*'''CTS G''' is a serine protease with activity similar to chymotrypsin C.<br />
-
<br />
+
*'''CTS K''' is a cysteine protease involved in bone resorption. For details see [[Cathepsin k]].<br />
-
<br />
+
*'''CTS S''' is a cysteine protease involved in degradation of antigenic proteins.<br />
-
<br />
+
*'''CTS X''' is a cysteine protease cleaving proteins at their C-terminus.<br />
-
<br />
+
-
== 3D Structures of Cathepsin ==
+
==Disease ==
 +
CTS B overexpression is associated with metastatic phenotypes in cancer. CTS C mutations are responsible for the Papillon-Lefevre syndrome. CTS K is involved in osteoporosis. CTS H overexpression is associated with prostate cancer. CTS L1 is implicated in myofibril necrosis.
-
=== Procathepsin-B ===
+
== Relevance ==
 +
CTS B breaks down proteins which are involved in amyloid plaques. CTS D is used as a breast cancer marker. CTS L is a potential drug target in cancer treatment. CTS L2 is expressed by cells of breast and colorectal carcinomas.
-
[[1pbh]], [[2pbh]], [[3pbh]] – hPCTSB - human<br />
+
== Structural highlights ==
-
[[1mir]] - rPCTSB (mutant) - rat
+
-
=== Cathepsin-B mature ===
+
CTS B is a cysteine protease. The <scene name='42/421669/Cv/11'>active site</scene> contains a <scene name='42/421669/Cv/13'>C26 residue from the N-terminal domain and H199 residue from the C-terminal domain</scene> (in cyan).<ref>PMID:21598397</ref>
-
 
+
-
 
+
-
[[3hhi]] – TbCTSB (mutant) residues 23-340+CA074 – ''Trypanosoma brucei''<br />
+
-
[[3k9m]] – hMCTSB+stefin A<br />
+
-
[[2ipp]], [[1huc]] – hMCTSB<br />
+
-
[[3cbj]], [[3cbk]] – hMCTSB (mutant)+chagasin<br />
+
-
[[2dc6]], [[2dc7]], [[2dc8]], [[2dc9]], [[2dca]], [[2dcb]], [[2dcc]], [[2dcd]] – bMCTSB+inhibitor – bovine<br />
+
-
[[1sp4]], [[1csb]] – bMCTSB+epoxysuccinyl inhibitor<br />
+
-
[[1ito]], [[1qdq]] – bMCTSB +inhibitor<br />
+
-
[[1gmy]] - bMCTSB +dipeptidyl nitrile<br />
+
-
[[1the]] – rMCTSB (mutant)+butanone inhibitor – rat<br />
+
-
[[1cpj]] - rMCTSB (mutant)<br />
+
-
[[1cte]] - rMCTSB+pyrimidine inhibitor<br />
+
-
 
+
-
 
+
-
=== Cathepsin-C mature ===
+
-
 
+
-
 
+
-
[[2djf]], [[2djg]] – hMCTSC +Gly-Phe-CHN2<br />
+
-
[[1jqp]] – rMCTSC<br />
+
-
[[1k3b]] – hMCTSC <br />
+
-
 
+
-
 
+
-
=== Cathepsin-D mature ===
+
-
 
+
-
 
+
-
[[1lyw]], [[1lya]] – hMCTSD <br />
+
-
[[1lyb]] - hMCTSD+pepstatin<br />
+
-
 
+
-
 
+
-
=== Cathepsin-E mature ===
+
-
 
+
-
 
+
-
[[1tzs]] – hMCTSE+activation peptide from CTSE<br />
+
-
 
+
-
 
+
-
=== Cathepsin-F mature ===
+
-
 
+
-
 
+
-
[[1m6d]] – hMCTSF+piperidine inhibitor<br />
+
-
 
+
-
 
+
-
=== Cathepsin-G mature ===
+
-
 
+
-
 
+
-
[[1kyn]] – hMCTSG +naphthalene inhibitor<br />
+
-
[[1au8]], [[1cgh]] - hMCTSG +phosphonate inhibitor<br />
+
-
[[1t32]] - hMCTSG +piperidine inhibitor
+
-
 
+
-
=== Cathepsin-H mature ===
+
-
 
+
-
[[1nb3]], [[1nb5]] – pMCTSH +stefin A – pig<br />
+
-
[[8pch]] - pMCTSH <br />
+
-
 
+
-
 
+
-
=== Cathepsin-K mature ===
+
-
 
+
-
 
+
-
[[3o1g]], [[3n3g]], [[2r6n]], [[1bgo]], [[3kwz]], [[3kx1]] – hMCTSK+ pyrimidine inhibitor<br />
+
-
[[3mpe]], [[3mpf]] – hMCTSK (mutant) + pyrimidine inhibitor<br />
+
-
[[3h7d]] - hMCTSK (mutant) + chondroitin-4-sulfate<br />
+
-
[[3c9e]] - hMCTSK + chondroitin-4-sulfate<br />
+
-
[[3kwb]] - hMCTSK (mutant)+dioxo-triazine<br />
+
-
[[3kw9]] - hMCTSK +triazine<br />
+
-
[[1yk8]] - hMCTSK + cyanamide inhibitor<br />
+
-
[[1yt7]] - hMCTSK + ketoamide inhibitor<br />
+
-
[[2aux]], [[2auz]] - hMCTSK + semicarbazone inhibitor<br />
+
-
[[1ayu]], [[1ayv]], [[1ayw]] - hMCTSK + carbohydrazide inhibitor<br />
+
-
[[2bdl]], [[1yk7]], [[1tu6]], [[1au3]], [[1au4]] - hMCTSK + pyrrolidine inhibitor<br />
+
-
[[1snk]] - hMCTSK + norleucine inhibitor<br />
+
-
[[1nl6]], [[1nlj]] - hMCTSK+ azepanone inhibitor<br />
+
-
[[1q6k]] - hMCTSK+carbamate inhibitor<br />
+
-
[[1au0]] - hMCTSK+ diacylaminoethyl ketone inhibitor<br />
+
-
[[1au2]] - hMCTSK+ propanone inhibitor<br />
+
-
[[1atk]] – hMCTSK+guanidine inhibitor<br />
+
-
[[1vsn]] - hMCTSK+ inhibitor<br />
+
-
[[2ato]] – hMCTSK+myocrisin<br />
+
-
[[1u9v]], [[1u9x]], [[1mem]] – hMCTSK+piperazine inhibitor<br />
+
-
[[1u9w]] - hMCTSK+imidazole inhibitor<br />
+
-
[[2ftd]] – MCTSK+azepan inhibitor – ''Macaca mulatta''<br />
+
-
[[2f7d]] – MCTSK (mutant)+nitrile inhibitor - rabbit<br />
+
-
 
+
-
===Procathepsin-L===
+
-
 
+
-
[[1cjl]], [[1cs8]] - hPCTS-L (mutant)
+
-
 
+
-
=== Cathepsin-L mature ===
+
-
 
+
-
 
+
-
[[3f75]] – MCTSL +CTSL propeptide – ''Toxoplasma gondii''<br />
+
-
[[2p86]] – TbMCTSL +K11002<br />
+
-
[[2nqd]] - CTSL residues 1-220 (mutant)+chagasin – ''Trypanosoma cruzi''<br />
+
-
[[1mhw]] – hMCTSL +tripeptide<br />
+
-
[[1icf]] – hMCTSL +MHC class II fragment<br />
+
-
 
+
-
 
+
-
=== Procathepsin-L1 ===
+
-
 
+
-
 
+
-
[[2o6x]] – hPCTSL1 (mutant) – ''Fasciola hepatica''<br />
+
-
 
+
-
 
+
-
=== Cathepsin-L1 mature ===
+
-
 
+
-
 
+
-
[[3iv2]] – hMCTSL1 (mutant) <br />
+
-
[[3k24]] - hMCTSL1 (mutant) +tripeptide<br />
+
-
[[2xu1]], [[2xu3]], [[2xu4]], [[2xu5]] - hMCTSL1 catalytic domain (mutant)+nitrile inhibitor<br />
+
-
[[3bc3]] - hMCTSL1 +inhibitor<br />
+
-
[[3h89]], [[3h8b]], [[3h8c]] - hMCTSL1 (mutant) + retro-binding inhibitor<br />
+
-
[[3hwn]], [[3hha]] – hMCTSL1+pyrazole inhibitor<br />
+
-
[[3kse]] – hMCTSL1 (mutant)+stefin
+
-
 
+
-
=== Cathepsin-L2 mature ===
+
-
 
+
-
 
+
-
[[3h6s]] – hMCTSL2+clitocypin<br />
+
-
[[1fh0]] – hMCTSL2 (mutant) +vinyl sulfone inhibitor<br />
+
-
[[3kfq]] - hMCTSL2 (mutant)+stefin
+
-
 
+
-
=== Procathepsin-S ===
+
-
 
+
-
 
+
-
[[2c0y]] – hPCTSS (mutant)<br />
+
-
 
+
-
 
+
-
=== Cathepsin-S mature ===
+
-
 
+
-
 
+
-
[[3n3g]] - hMCTSS+ pyrimidine inhibitor<br />
+
-
[[3ovx]] - hMCTSS+ aldehyde inhibitor<br />
+
-
[[3ovz]] - hMCTSS+ ketoamide inhibitor<br />
+
-
[[3kwn]] – hMCTSS (mutant)+ thioether acetamide<br />
+
-
[[3iej]] - hMCTSS (mutant)+pyrazole inhibitor<br />
+
-
[[2h7j]], [[2hxz]]- hMCTSS+triazole inhibitor<br />
+
-
[[2r9m]], [[2r9n]], [[2r9o]] – hMCTSS+piperidine inhibitor<br />
+
-
[[2op3]], [[2hhn]], [[2g7y]], [[2hh5]], [[2f1g]] – hMCTSS+aryl inhibitor<br />
+
-
[[2fud]], [[2fra]], [[2frq]], [[2ft2]], [[1npz]], [[1nqc]] – hMCTSS+inhibitor<br />
+
-
[[2fye]], [[2g6d]] – hMCTSS (mutant)+inhibitor<br />
+
-
[[2fq9]], [[1ms6]] – hMCTSS +nitrile inhibitor<br />
+
-
[[1glo]] - hMCTSS (mutant)<br />
+
-
 
+
-
 
+
-
=== Procathepsin-X ===
+
-
 
+
-
 
+
-
[[1deu]] - hPCTSX<br />
+
 +
== 3D Structures of Cathepsin ==
 +
[[Cathepsin 3D structures]]
-
=== Cathepsin-X mature ===
+
</StructureSection>
-
[[1ef7]] – hMCTSX<br />
+
== References ==
 +
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

human cathepsin B complex with inhibitor 3ai8

Drag the structure with the mouse to rotate


References

  1. ↑ Nomura T, Katunuma N. Involvement of cathepsins in the invasion, metastasis and proliferation of cancer cells. J Med Invest. 2005 Feb;52(1-2):1-9. PMID:15751268
  2. ↑ Mirkovic B, Renko M, Turk S, Sosic I, Jevnikar Z, Obermajer N, Turk D, Gobec S, Kos J. Novel Mechanism of Cathepsin B Inhibition by Antibiotic Nitroxoline and Related Compounds. ChemMedChem. 2011 May 20. doi: 10.1002/cmdc.201100098. PMID:21598397 doi:10.1002/cmdc.201100098

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

Retrieved from "http://52.214.119.220/wiki/index.php/Cathepsin"
Personal tools