Cathepsin

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[[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]].
[[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]].
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*'''CTS B, F, H, L, L1, L2''' are cysteine proteases.<br />
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*'''CTS B, F, H, L, L1, L2 or V''' are cysteine proteases.<br />
*'''CTS D, E''' are aspartyl proteases which degrade insulin.<br />
*'''CTS D, E''' are aspartyl proteases which degrade insulin.<br />
*'''CTS G''' is a serine protease with activity similar to chymotrypsin C.<br />
*'''CTS G''' is a serine protease with activity similar to chymotrypsin C.<br />
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</StructureSection>
</StructureSection>
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== 3D Structures of Cathepsin ==
 
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
 
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{{#tree:id=OrganizedByTopic|openlevels=0|
 
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* Procathepsin-A (Lysosomal protective protein)
 
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**[[4ci9]], [[1ivy]], [[4mws]], [[4mwt]] - hCTSB – human<br />
 
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**[[4cia]], [[4cib]] - hCTSB + inhibitor<br />
 
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* Procathepsin-B
 
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**[[1pbh]], [[2pbh]], [[3pbh]] – hPCTSB <br />
 
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**[[1mir]] - rPCTSB (mutant) - rat<br />
 
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**[[4n4z]], [[4hwy]] - TbCTSB – ''Trypanosoma brucei''<br />
 
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**[[5fpw]] – TbCTSB (mutant)<br />
 
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* Cathepsin-B mature
 
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**[[2ipp]], [[1huc]] – hMCTSB<br />
 
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**[[3k9m]] – hMCTSB+stefin A<br />
 
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**[[3ai8]] – hMCTSB + antibiotic<br />
 
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**[[3cbj]], [[3cbk]] – hMCTSB (mutant)+chagasin<br />
 
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**[[5mbl]], [[5mbm]] – hMCTSB + darpin <br />
 
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**[[6ay2]] – hMCTSB + inhibitor <br />
 
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**[[2dc6]], [[2dc7]], [[2dc8]], [[2dc9]], [[2dca]], [[2dcb]], [[2dcc]], [[2dcd]] – bMCTSB+inhibitor – bovine<br />
 
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**[[1sp4]], [[1csb]] – bMCTSB+epoxysuccinyl inhibitor<br />
 
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**[[1ito]], [[1qdq]] – bMCTSB +inhibitor<br />
 
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**[[1gmy]] - bMCTSB +dipeptidyl nitrile<br />
 
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**[[1the]] – rMCTSB (mutant)+butanone inhibitor – rat<br />
 
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**[[1cpj]] - rMCTSB (mutant)<br />
 
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**[[1cte]] - rMCTSB+pyrimidine inhibitor<br />
 
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**[[3hhi]] – TbCTSB (mutant) residues 23-340+CA074 <br />
 
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**[[3mor]] - TbCTSB residues 23-340<br />
 
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**[[3qsd]], [[3s3q]], [[3s3r]] - CTSB (mutant) residues 87-340+ inhibitor – ''Schistosoma mansoni''<br />
 
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* Cathepsin-C mature or [[Dipeptidyl peptidase]]-I
 
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**[[1k3b]] – hMCTSC <br />
 
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**[[2djf]], [[2djg]], [[4oel]], [[4oem]] – hMCTSC + dipeptide<br />
 
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**[[3pdf]], [[4cdc]], [[4cdd]], [[4cde]], [[4cdf]] – hMCTSC + inhibitor<br />
 
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**[[1jqp]] – rMCTSC <br />
 
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* Cathepsin-D mature
 
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**[[1lyw]], [[1lya]] – hMCTSD <br />
 
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**[[1lyb]] - hMCTSD+pepstatin<br />
 
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**[[4obz]], [[4oc6]], [[4od9]] – hMCTSD + non-peptidic inhibitor<br />
 
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**[[5ux4]] – rMCTSD + inhibitor<br />
 
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* Cathepsin-E mature
 
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**[[1tzs]] – hMCTSE+activation peptide from CTSE<br />
 
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* Cathepsin-F mature
 
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**[[1m6d]] – hMCTSF+piperidine inhibitor<br />
 
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* Cathepsin-G mature
 
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**[[1kyn]] – hMCTSG +naphthalene inhibitor<br />
 
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**[[1au8]], [[1cgh]] - hMCTSG +phosphonate inhibitor<br />
 
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**[[1t32]] - hMCTSG +piperidine inhibitor
 
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*Procathepsin-H
 
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**[[6czk]] – hPCTSH <br />
 
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**[[6czs]] – hPCTSH (mutant) <br />
 
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* Cathepsin-H mature
 
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**[[1nb3]], [[1nb5]] – pMCTSH +stefin A – pig<br />
 
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**[[8pch]] - pMCTSH <br />
 
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* Procathepsin-K
 
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**[[1by8]], [[7pck]] – hPCTSK<br />
 
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* Cathepsin-K mature
 
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**[[4n79]], [[5tun]], [[4yva]] – hMCTSK<br />
 
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**[[5jh3]], [[5z5o]] – hMCTSK (mutant) <br />
 
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**[[3o1g]], [[3n3g]], [[2r6n]], [[1bgo]], [[3kwz]], [[3kx1]], [[3o0u]] – hMCTSK+ pyrimidine inhibitor<br />
 
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**[[5qby]], [[5qbv]] – hMCTSK (mutant) + pyrimidine inhibitor<br />
 
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**[[3h7d]] - hMCTSK (mutant) + chondroitin-4-sulfate<br />
 
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**[[3c9e]], [[4n8w]] - hMCTSK + chondroitin-4-sulfate<br />
 
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**[[3kwb]] - hMCTSK (mutant)+dioxo-triazine<br />
 
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**[[3kw9]] - hMCTSK +triazine<br />
 
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**[[1yk8]] - hMCTSK + cyanamide inhibitor<br />
 
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**[[1yt7]] - hMCTSK + ketoamide inhibitor<br />
 
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**[[4x6j]] - hMCTSK + benzamide inhibitor<br />
 
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**[[2aux]], [[2auz]] - hMCTSK + semicarbazone inhibitor<br />
 
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**[[1ayu]], [[1ayv]], [[1ayw]] - hMCTSK + carbohydrazide inhibitor<br />
 
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**[[2bdl]], [[1yk7]], [[1tu6]], [[1au3]], [[1au4]], [[4dmx]], [[4dmy]] - hMCTSK + pyrrolidine inhibitor<br />
 
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**[[1snk]] - hMCTSK + norleucine inhibitor<br />
 
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**[[1nl6]], [[1nlj]] - hMCTSK+ azepanone inhibitor<br />
 
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**[[1q6k]] - hMCTSK+carbamate inhibitor<br />
 
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**[[1au0]] - hMCTSK+ diacylaminoethyl ketone inhibitor<br />
 
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**[[1au2]] - hMCTSK+ propanone inhibitor<br />
 
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**[[1atk]] – hMCTSK+guanidine inhibitor<br />
 
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**[[1vsn]], [[5j94]], [[4x6h]], [[4x6i]], [[6qbs]] - hMCTSK+ inhibitor<br />
 
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**[[6ash]] – hMCTSK (mutant) + inhibitor<br />
 
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**[[2ato]] – hMCTSK+myocrisin<br />
 
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**[[1u9v]], [[1u9x]], [[1mem]] – hMCTSK+piperazine inhibitor<br />
 
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**[[1u9w]] - hMCTSK+imidazole inhibitor<br />
 
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**[[5tdi]], [[4yv8]] – hMCTSK + odanacatib<br />
 
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**[[5tdi]] – hMCTSK + lichostatinal<br />
 
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**[[5ja7]] – hMCTSK (mutant) + effector<br />
 
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**[[2ftd]] – MCTSK+azepan inhibitor – ''Macaca mulatta''<br />
 
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**[[2f7d]] – MCTSK (mutant)+nitrile inhibitor - rabbit<br />
 
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**[[5t6u]] – mMCTSK<br />
 
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**[[6bki]] – mMCTSK (mutant) <br />
 
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*Procathepsin-L
 
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**[[1cjl]], [[1cs8]] - hPCTS-L (mutant)<br />
 
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**[[3qj3]] - PCTS-L (mutant) – ''Tenebrio molitor''<br />
 
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* Cathepsin-L mature
 
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**[[4axl]] – hMCTSL catalytic domain<br />
 
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**[[4axm]] – hMCTSL catalytic domain + inhibitor<br />
 
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**[[1mhw]] – hMCTSL +tripeptide<br />
 
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**[[1icf]] – hMCTSL +MHC class II fragment<br />
 
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**[[3f75]] – MCTSL +CTSL propeptide – ''Toxoplasma gondii''<br />
 
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**[[2p86]] – TbMCTSL +K11002<br />
 
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**[[2nqd]] - CTSL residues 1-220 (mutant)+chagasin – ''Trypanosoma cruzi''<br />
 
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* Procathepsin-L1
 
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**[[2o6x]] – hPCTSL1 (mutant) – ''Fasciola hepatica''<br />
 
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* Cathepsin-L1 mature
 
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**[[4axl]] – hMCTSL1 catalytic domain<br />
 
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**[[3iv2]], [[5i4h]] – hMCTSL1 (mutant) <br />
 
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**[[3k24]] - hMCTSL1 (mutant) +tripeptide<br />
 
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**[[3of8]] - hMCTSL1 + dipeptidyl inhibitor<br />
 
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**[[2xu1]], [[2xu3]], [[2xu4]], [[2xu5]], [[2yj2]], [[2yj8]], [[2yj9]], [[2yjb]], [[2yjc]] - hMCTSL1 catalytic domain (mutant)+nitrile inhibitor<br />
 
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**[[3h89]], [[3h8b]], [[3h8c]] - hMCTSL1 (mutant) + retro-binding inhibitor<br />
 
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**[[3hwn]], [[3hha]] – hMCTSL1+pyrazole inhibitor<br />
 
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**[[5mqy]] – hMCTSL1 + pyrimidine inhibitor<br />
 
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**[[3kse]] – hMCTSL1 (mutant)+stefin<br />
 
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**[[4axm]], [[5mae]], [[5maj]], [[5f02]], [[3bc3]], [[3of9]] – hMCTSL1 catalytic domain + inhibitor<br />
 
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**[[6f06]], [[6ezx]], [[6ezp]] – hMCTSL1 catalytic domain + carboxamide inhibitor<br />
 
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* Cathepsin-L2 mature
 
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**[[3h6s]] – hMCTSL2+clitocypin<br />
 
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**[[1fh0]] – hMCTSL2 (mutant) +vinyl sulfone inhibitor<br />
 
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**[[3kfq]] - hMCTSL2 (mutant)+stefin
 
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* Procathepsin-S
 
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**[[2c0y]] – hPCTSS (mutant)<br />
 
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* Cathepsin-S mature
 
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**[[3n3g]], [[3n4c]] - hMCTSS+ pyrimidine inhibitor<br />
 
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**[[3ovx]] - hMCTSS+ aldehyde inhibitor<br />
 
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**[[3ovz]] - hMCTSS+ ketoamide inhibitor<br />
 
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**[[5qc4]] – hMCTSS (mutant)+ thioether acetamide<br />
 
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**[[3iej]], [[5qcf]], [[5qce]], [[5qcd]], [[5qcc]], [[5qcg]], [[5qch]], [[5qci]] - hMCTSS (mutant)+pyrazole inhibitor<br />
 
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**[[2h7j]], [[2hxz]]- hMCTSS+triazole inhibitor<br />
 
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**[[2r9m]], [[2r9n]], [[2r9o]], [[5qcj]] – hMCTSS+piperidine inhibitor<br />
 
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**[[5qbu]], [[5qbw]], [[5qbx]], [[5qbz]], [[5qc0]], [[5qc1]], [[5qc2]], [[5qc3]], [[5qc5]], [[5qc6]], [[5qc7]], [[5qc8]], [[5qc9]], [[5qca]], [[5qcb]] – hMCTSS (mutant) + piperidine inhibitor<br />
 
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**[[2op3]], [[2hhn]], [[2g7y]], [[2hh5]], [[2f1g]] – hMCTSS+aryl inhibitor<br />
 
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**[[2fud]], [[2fra]], [[2frq]], [[2ft2]], [[1npz]], [[1nqc]], [[4p6e]], [[4p6g]] – hMCTSS+inhibitor<br />
 
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**[[2fye]], [[2g6d]] – hMCTSS (mutant)+inhibitor<br />
 
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**[[2fq9]], [[1ms6]] – hMCTSS +nitrile inhibitor<br />
 
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**[[1glo]] - hMCTSS (mutant)<br />
 
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**[[4bs5]], [[4mzo]], [[4mzs]] - mMCTSS+ pyrrolidine inhibitor<br />
 
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**[[4bsq]] - mMCTSS+ morpholine inhibitor<br />
 
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**[[4bpv]], [[4bqv]], [[4bs6]] - mMCTSS +nitrile inhibitor<br />
 
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* Procathepsin-X
 
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**[[1deu]] - hPCTSX<br />
 
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* Cathepsin-X mature
 
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**[[1ef7]] – hMCTSX<br />
 
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}}
 
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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

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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