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- PDB-8he9: Crystal structure of CTSB in complex with K777 -

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Basic information

Entry
Database: PDB / ID: 8he9
TitleCrystal structure of CTSB in complex with K777
ComponentsCathepsin B
KeywordsANTIVIRAL PROTEIN/INHIBITOR / inhibitor / antiviral / protease / ANTIVIRAL PROTEIN / ANTIVIRAL PROTEIN-INHIBITOR complex
Function / homology
Function and homology information


cathepsin B / peptidase inhibitor complex / endolysosome lumen / thyroid hormone generation / cellular response to thyroid hormone stimulus / Trafficking and processing of endosomal TLR / proteoglycan binding / Assembly of collagen fibrils and other multimeric structures / Collagen degradation / collagen catabolic process ...cathepsin B / peptidase inhibitor complex / endolysosome lumen / thyroid hormone generation / cellular response to thyroid hormone stimulus / Trafficking and processing of endosomal TLR / proteoglycan binding / Assembly of collagen fibrils and other multimeric structures / Collagen degradation / collagen catabolic process / decidualization / collagen binding / epithelial cell differentiation / MHC class II antigen presentation / cysteine-type peptidase activity / proteolysis involved in protein catabolic process / melanosome / peptidase activity / : / regulation of apoptotic process / ficolin-1-rich granule lumen / lysosome / apical plasma membrane / symbiont entry into host cell / external side of plasma membrane / cysteine-type endopeptidase activity / Neutrophil degranulation / perinuclear region of cytoplasm / proteolysis / extracellular space / extracellular exosome / extracellular region
Similarity search - Function
Peptidase C1A, propeptide / Peptidase family C1 propeptide / Cysteine peptidase, asparagine active site / Eukaryotic thiol (cysteine) proteases asparagine active site. / Cysteine peptidase, histidine active site / Eukaryotic thiol (cysteine) proteases histidine active site. / : / Peptidase C1A, papain C-terminal / Papain family cysteine protease / Papain family cysteine protease ...Peptidase C1A, propeptide / Peptidase family C1 propeptide / Cysteine peptidase, asparagine active site / Eukaryotic thiol (cysteine) proteases asparagine active site. / Cysteine peptidase, histidine active site / Eukaryotic thiol (cysteine) proteases histidine active site. / : / Peptidase C1A, papain C-terminal / Papain family cysteine protease / Papain family cysteine protease / Cysteine peptidase, cysteine active site / Eukaryotic thiol (cysteine) proteases cysteine active site. / Papain-like cysteine peptidase superfamily
Similarity search - Domain/homology
Chem-0IW / Cathepsin B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.55 Å
AuthorsWang, H. / Li, D. / Sun, L. / Yang, H.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)92169109 China
CitationJournal: Nat Commun / Year: 2023
Title: Structure-based discovery of dual pathway inhibitors for SARS-CoV-2 entry.
Authors: Wang, H. / Yang, Q. / Liu, X. / Xu, Z. / Shao, M. / Li, D. / Duan, Y. / Tang, J. / Yu, X. / Zhang, Y. / Hao, A. / Wang, Y. / Chen, J. / Zhu, C. / Guddat, L. / Chen, H. / Zhang, L. / Chen, X. ...Authors: Wang, H. / Yang, Q. / Liu, X. / Xu, Z. / Shao, M. / Li, D. / Duan, Y. / Tang, J. / Yu, X. / Zhang, Y. / Hao, A. / Wang, Y. / Chen, J. / Zhu, C. / Guddat, L. / Chen, H. / Zhang, L. / Chen, X. / Jiang, B. / Sun, L. / Rao, Z. / Yang, H.
History
DepositionNov 7, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 13, 2023Provider: repository / Type: Initial release
Revision 1.1Jun 19, 2024Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Oct 30, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Cathepsin B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)28,8115
Polymers27,9721
Non-polymers8394
Water2,342130
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)31.432, 70.497, 93.739
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

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Components

#1: Protein Cathepsin B / APP secretase / APPS / Cathepsin B1


Mass: 27972.156 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CTSB, CPSB / Production host: Escherichia coli (E. coli) / References: UniProt: P07858, cathepsin B
#2: Chemical ChemComp-0IW / Nalpha-[(4-methylpiperazin-1-yl)carbonyl]-N-[(3S)-1-phenyl-5-(phenylsulfonyl)pentan-3-yl]-L-phenylalaninamide / APC-3316, bound form / 4-Methylpiperazine-1-carboxylic acid [1-[(3-benzenesulfonyl-1-phenethylallyl)carbamoyl]-2-phenylethyl]amide, bound form


Type: peptide-like / Mass: 576.749 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C32H40N4O4S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 130 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 1.86 Å3/Da / Density % sol: 33.74 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: 17.1 % v/v Polyethylene glycol 600, 50 mM MES pH 5.6, 8.6 % w/v Polyethylene glycol 4,000

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9537 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Aug 10, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9537 Å / Relative weight: 1
ReflectionResolution: 1.55→39.03 Å / Num. obs: 31146 / % possible obs: 99.9 % / Redundancy: 13.26 % / CC1/2: 1 / Rmerge(I) obs: 0.057 / Rrim(I) all: 0.06 / Net I/σ(I): 23.75
Reflection shell
Resolution (Å)Rmerge(I) obsNum. unique obsCC1/2Rrim(I) allDiffraction-ID
1.55-1.640.8749250.9550.9041
1.64-1.760.51946680.9830.5391
1.76-1.90.32243330.9920.3351
1.9-2.080.17640260.9970.1831
2.08-2.320.10536410.9990.1091
2.32-2.680.0732660.9990.0731
2.68-3.280.04627850.9990.0471
3.28-4.620.029219310.031
4.62-39.030.025130810.0261

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Processing

Software
NameVersionClassification
XDS2020-12-02data scaling
PHENIX1.20.1-4487-000refinement
PDB_EXTRACT3.27data extraction
XDS2020-12-02data reduction
PHENIX1.20.1-4487-000phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6AY2

6ay2


Resolution: 1.55→39.03 Å / SU ML: 0.18 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 25.77 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.202 1996 6.42 %
Rwork0.1794 --
obs0.1809 31071 99.62 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.55→39.03 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1931 0 57 130 2118
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0062058
X-RAY DIFFRACTIONf_angle_d0.9142799
X-RAY DIFFRACTIONf_dihedral_angle_d9.387307
X-RAY DIFFRACTIONf_chiral_restr0.062277
X-RAY DIFFRACTIONf_plane_restr0.009367
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.55-1.590.32171380.31681997X-RAY DIFFRACTION98
1.59-1.630.29941380.29412026X-RAY DIFFRACTION100
1.63-1.680.29171410.26482053X-RAY DIFFRACTION100
1.68-1.730.27411390.23442040X-RAY DIFFRACTION99
1.73-1.790.25811410.21962046X-RAY DIFFRACTION100
1.79-1.870.24681400.20292057X-RAY DIFFRACTION100
1.87-1.950.23881420.20582053X-RAY DIFFRACTION100
1.95-2.050.20151410.17882053X-RAY DIFFRACTION100
2.05-2.180.18641430.17442072X-RAY DIFFRACTION100
2.18-2.350.23121430.17862093X-RAY DIFFRACTION100
2.35-2.590.21961430.18672073X-RAY DIFFRACTION100
2.59-2.960.20521460.18282129X-RAY DIFFRACTION100
2.96-3.730.17111460.16342123X-RAY DIFFRACTION100
3.73-39.030.17221550.15212260X-RAY DIFFRACTION100
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.94061.3635-0.12534.6481.04641.82550.3146-0.2853-0.26130.9341-0.1728-0.38870.08940.1211-0.07310.2859-0.04-0.06820.19830.01720.1984-7.1868-6.391612.0274
23.2967-1.54521.25494.1711-1.06732.3990.3503-0.14360.39190.5042-0.40890.2113-0.37450.00920.11130.7074-0.14490.11920.4853-0.05450.3802-13.08989.701419.9748
32.1910.8877-1.0251.6021-0.09993.65960.3812-0.2707-0.6611.0637-0.1502-0.7184-0.03010.0217-0.20730.67-0.0446-0.27280.26460.12660.4722-2.2208-12.657516.2273
41.74130.5642-0.2213.76940.02871.85440.06040.09530.0915-0.0025-0.00640.1004-0.1835-0.0843-0.05650.15180.0010.01450.18940.00150.1698-9.60795.4923-0.514
52.9037-1.98162.07233.7652-4.72596.31120.0077-0.0521-0.353-0.19720.1655-0.32740.3556-0.0525-0.03570.18160.0098-0.0150.2356-0.0410.3143-0.557-8.51813.5055
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 0 through 105 )
2X-RAY DIFFRACTION2chain 'A' and (resid 106 through 127 )
3X-RAY DIFFRACTION3chain 'A' and (resid 128 through 156 )
4X-RAY DIFFRACTION4chain 'A' and (resid 157 through 241 )
5X-RAY DIFFRACTION5chain 'A' and (resid 242 through 254 )

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