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Yorodumi- PDB-8oza: Human cathepsin L in complex with covalently bound CA-074 methyl ester -
+Open data
-Basic information
Entry | Database: PDB / ID: 8oza | ||||||||||||||||||
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Title | Human cathepsin L in complex with covalently bound CA-074 methyl ester | ||||||||||||||||||
Components | Cathepsin L | ||||||||||||||||||
Keywords | HYDROLASE / cystein protease / drug target / lysosome / epoxide | ||||||||||||||||||
Function / homology | Function and homology information enkephalin processing / cathepsin L / CD4-positive, alpha-beta T cell lineage commitment / macrophage apoptotic process / chromaffin granule / elastin catabolic process / antigen processing and presentation of peptide antigen / RUNX1 regulates transcription of genes involved in differentiation of keratinocytes / endolysosome lumen / cellular response to thyroid hormone stimulus ...enkephalin processing / cathepsin L / CD4-positive, alpha-beta T cell lineage commitment / macrophage apoptotic process / chromaffin granule / elastin catabolic process / antigen processing and presentation of peptide antigen / RUNX1 regulates transcription of genes involved in differentiation of keratinocytes / endolysosome lumen / cellular response to thyroid hormone stimulus / Trafficking and processing of endosomal TLR / zymogen activation / proteoglycan binding / Assembly of collagen fibrils and other multimeric structures / antigen processing and presentation / cysteine-type endopeptidase activator activity involved in apoptotic process / fibronectin binding / protein autoprocessing / Collagen degradation / collagen catabolic process / serpin family protein binding / cysteine-type peptidase activity / Attachment and Entry / endocytic vesicle lumen / collagen binding / MHC class II antigen presentation / Degradation of the extracellular matrix / multivesicular body / lysosomal lumen / proteolysis involved in protein catabolic process / Endosomal/Vacuolar pathway / positive regulation of apoptotic signaling pathway / antigen processing and presentation of exogenous peptide antigen via MHC class II / histone binding / collagen-containing extracellular matrix / adaptive immune response / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / lysosome / symbiont entry into host cell / immune response / apical plasma membrane / fusion of virus membrane with host plasma membrane / cysteine-type endopeptidase activity / intracellular membrane-bounded organelle / fusion of virus membrane with host endosome membrane / Golgi apparatus / proteolysis / extracellular space / extracellular exosome / extracellular region / nucleus / plasma membrane Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.8 Å | ||||||||||||||||||
Authors | Falke, S. / Lieske, J. / Guenther, S. / Ewert, W. / Reinke, P.Y.A. / Loboda, J. / Karnicar, K. / Usenik, A. / Lindic, N. / Sekirnik, A. ...Falke, S. / Lieske, J. / Guenther, S. / Ewert, W. / Reinke, P.Y.A. / Loboda, J. / Karnicar, K. / Usenik, A. / Lindic, N. / Sekirnik, A. / Chapman, H.N. / Hinrichs, W. / Turk, D. / Meents, A. | ||||||||||||||||||
Funding support | Germany, Slovenia, 5items
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Citation | Journal: J.Med.Chem. / Year: 2024 Title: Structural Elucidation and Antiviral Activity of Covalent Cathepsin L Inhibitors. Authors: Falke, S. / Lieske, J. / Herrmann, A. / Loboda, J. / Karnicar, K. / Gunther, S. / Reinke, P.Y.A. / Ewert, W. / Usenik, A. / Lindic, N. / Sekirnik, A. / Dretnik, K. / Tsuge, H. / Turk, V. / ...Authors: Falke, S. / Lieske, J. / Herrmann, A. / Loboda, J. / Karnicar, K. / Gunther, S. / Reinke, P.Y.A. / Ewert, W. / Usenik, A. / Lindic, N. / Sekirnik, A. / Dretnik, K. / Tsuge, H. / Turk, V. / Chapman, H.N. / Hinrichs, W. / Ebert, G. / Turk, D. / Meents, A. | ||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8oza.cif.gz | 195.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8oza.ent.gz | 153.5 KB | Display | PDB format |
PDBx/mmJSON format | 8oza.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8oza_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 8oza_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8oza_validation.xml.gz | 38.2 KB | Display | |
Data in CIF | 8oza_validation.cif.gz | 53.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/oz/8oza ftp://data.pdbj.org/pub/pdb/validation_reports/oz/8oza | HTTPS FTP |
-Related structure data
Related structure data | 7qkdC 7zs7C 7zvfC 7zxaC 8a4uC 8a4vC 8a4wC 8a4xC 8a5bC 8ahvC 8b4fC 8c77C 8ofaC 8prxC 8qkbC C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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3 |
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4 |
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Unit cell |
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-Components
-Protein , 1 types, 4 molecules ABCD
#1: Protein | Mass: 24161.676 Da / Num. of mol.: 4 / Mutation: T110A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CTSL, CTSL1 / Production host: Komagataella phaffii GS115 (fungus) / References: UniProt: P07711 |
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-Non-polymers , 6 types, 478 molecules
#2: Chemical | ChemComp-WRH / #3: Chemical | ChemComp-PEG / #4: Chemical | ChemComp-EDO / #5: Chemical | ChemComp-ACT / | #6: Chemical | ChemComp-DMS / | #7: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.06 Å3/Da / Density % sol: 40.2 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: Mature cathepsin L at a concentration of 7 mg/ml was equilibrated against 27% w/v PEG 8000, 1 mM TCEP and 0.1 M sodium acetate at pH 4.0. Crystals, which grew at 293 K to final size after ...Details: Mature cathepsin L at a concentration of 7 mg/ml was equilibrated against 27% w/v PEG 8000, 1 mM TCEP and 0.1 M sodium acetate at pH 4.0. Crystals, which grew at 293 K to final size after approximately 3 days, were transferred to a compound soaking solution containing 22% w/v PEG 8000, 1 mM TCEP and 0.1 M sodium acetate at pH 4.0 as well as 5% v/v DMSO and 10% v/v PEG 400. |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: PETRA III, DESY / Beamline: P11 / Wavelength: 1.033 Å |
Detector | Type: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Oct 3, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.033 Å / Relative weight: 1 |
Reflection | Resolution: 1.8→49.51 Å / Num. obs: 69325 / % possible obs: 94.3 % / Redundancy: 10.5 % / Biso Wilson estimate: 19.04 Å2 / CC1/2: 0.995 / Rrim(I) all: 0.261 / Net I/σ(I): 9.09 |
Reflection shell | Resolution: 1.8→1.85 Å / Mean I/σ(I) obs: 1.97 / Num. unique obs: 5241 / CC1/2: 0.755 / % possible all: 90.1 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.8→49.51 Å / SU ML: 0.1917 / Cross valid method: FREE R-VALUE / σ(F): 1.96 / Phase error: 21.0063 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 22.8 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.8→49.51 Å
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Refine LS restraints |
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LS refinement shell |
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