[English] 日本語
Yorodumi
- PDB-8rnd: Cathepsin S in complex with NNPI-C10 inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8rnd
TitleCathepsin S in complex with NNPI-C10 inhibitor
Components
  • Cathepsin S
  • NNPI-C10 inhibitor
KeywordsONCOPROTEIN / Protease / Inhibitor / Complex / Cathepsin
Function / homology
Function and homology information


cathepsin S / basement membrane disassembly / positive regulation of cation channel activity / antigen processing and presentation of peptide antigen / endolysosome lumen / response to acidic pH / cellular response to thyroid hormone stimulus / Trafficking and processing of endosomal TLR / proteoglycan binding / Assembly of collagen fibrils and other multimeric structures ...cathepsin S / basement membrane disassembly / positive regulation of cation channel activity / antigen processing and presentation of peptide antigen / endolysosome lumen / response to acidic pH / cellular response to thyroid hormone stimulus / Trafficking and processing of endosomal TLR / proteoglycan binding / Assembly of collagen fibrils and other multimeric structures / toll-like receptor signaling pathway / antigen processing and presentation / cysteine-type endopeptidase activator activity involved in apoptotic process / fibronectin binding / collagen catabolic process / extracellular matrix disassembly / laminin binding / collagen binding / MHC class II antigen presentation / phagocytic vesicle / Degradation of the extracellular matrix / lysosomal lumen / proteolysis involved in protein catabolic process / Endosomal/Vacuolar pathway / positive regulation of apoptotic signaling pathway / protein processing / antigen processing and presentation of exogenous peptide antigen via MHC class II / late endosome / tertiary granule lumen / collagen-containing extracellular matrix / adaptive immune response / ficolin-1-rich granule lumen / lysosome / immune response / cysteine-type endopeptidase activity / intracellular membrane-bounded organelle / serine-type endopeptidase activity / Neutrophil degranulation / proteolysis / extracellular space / extracellular region
Similarity search - Function
Cathepsin propeptide inhibitor domain (I29) / Cathepsin propeptide inhibitor domain (I29) / Cathepsin propeptide inhibitor domain (I29) / Papain-like cysteine endopeptidase / : / 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 ...Cathepsin propeptide inhibitor domain (I29) / Cathepsin propeptide inhibitor domain (I29) / Cathepsin propeptide inhibitor domain (I29) / Papain-like cysteine endopeptidase / : / 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
NITRATE ION / DI(HYDROXYETHYL)ETHER / TRIETHYLENE GLYCOL / Cathepsin S
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.56 Å
AuthorsPetruzzella, A. / Lau, K. / Pojer, F. / Oricchio, E.
Funding support Switzerland, 1items
OrganizationGrant numberCountry
Swiss Cancer LeagueKFS-5102-08-2020 Switzerland
CitationJournal: Nat.Chem.Biol. / Year: 2024
Title: Antibody-peptide conjugates deliver covalent inhibitors blocking oncogenic cathepsins.
Authors: Petruzzella, A. / Bruand, M. / Santamaria-Martinez, A. / Katanayeva, N. / Reymond, L. / Wehrle, S. / Georgeon, S. / Inel, D. / van Dalen, F.J. / Viertl, D. / Lau, K. / Pojer, F. / ...Authors: Petruzzella, A. / Bruand, M. / Santamaria-Martinez, A. / Katanayeva, N. / Reymond, L. / Wehrle, S. / Georgeon, S. / Inel, D. / van Dalen, F.J. / Viertl, D. / Lau, K. / Pojer, F. / Schottelius, M. / Zoete, V. / Verdoes, M. / Arber, C. / Correia, B.E. / Oricchio, E.
History
DepositionJan 9, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 5, 2024Provider: repository / Type: Initial release
Revision 1.1Jun 12, 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.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cathepsin S
B: NNPI-C10 inhibitor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)26,55910
Polymers25,9002
Non-polymers6598
Water1,982110
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: mass spectrometry
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3390 Å2
ΔGint13 kcal/mol
Surface area10200 Å2
MethodPISA
Unit cell
Length a, b, c (Å)44.633, 129.220, 37.670
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212
Space group name HallP22ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x+1/2,y+1/2,-z
#4: -x,-y,z
Components on special symmetry positions
IDModelComponents
11A-559-

HOH

-
Components

-
Protein / Protein/peptide , 2 types, 2 molecules AB

#1: Protein Cathepsin S


Mass: 24689.689 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CTSS / Cell line (production host): ExpiCHO / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P25774, cathepsin S
#2: Protein/peptide NNPI-C10 inhibitor


Mass: 1210.500 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)

-
Non-polymers , 6 types, 118 molecules

#3: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Formula: C2H6O2
#4: Chemical ChemComp-PGE / TRIETHYLENE GLYCOL


Mass: 150.173 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Formula: C6H14O4
#5: Chemical ChemComp-NO3 / NITRATE ION


Mass: 62.005 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: NO3
#6: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#7: Chemical ChemComp-PEG / DI(HYDROXYETHYL)ETHER


Mass: 106.120 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H10O3
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 110 / Source method: isolated from a natural source / Formula: H2O

-
Details

Compound detailsCovalently-bound inhibitor for Cathepsin S
Has ligand of interestN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.2 Å3/Da / Density % sol: 44.09 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop
Details: 0.1M BisTris Propane pH 6.5, 0.2 M NaNO3, 20% w/v PEG3350, 10% ethylene glycol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1.000002 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 18, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.000002 Å / Relative weight: 1
ReflectionResolution: 1.56→42.19 Å / Num. obs: 60215 / % possible obs: 99.8 % / Redundancy: 5.7 % / Biso Wilson estimate: 15.95 Å2 / CC1/2: 0.997 / Rrim(I) all: 0.143 / Net I/σ(I): 8.67
Reflection shellResolution: 1.56→1.64 Å / Redundancy: 5.4 % / Mean I/σ(I) obs: 1.31 / Num. unique obs: 9679 / CC1/2: 0.665 / Rrim(I) all: 1.46 / % possible all: 99.7

-
Processing

Software
NameVersionClassification
PHENIXdev_5246refinement
PHASERphasing
XDSdata reduction
Aimlessdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.56→42.19 Å / SU ML: 0.1706 / Cross valid method: FREE R-VALUE / σ(F): 1.92 / Phase error: 25.6237
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2251 3019 5.02 %
Rwork0.1708 57108 -
obs0.1735 60127 99.71 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 27.96 Å2
Refinement stepCycle: LAST / Resolution: 1.56→42.19 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1743 0 90 110 1943
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00921873
X-RAY DIFFRACTIONf_angle_d1.12192511
X-RAY DIFFRACTIONf_chiral_restr0.0511251
X-RAY DIFFRACTIONf_plane_restr0.0072323
X-RAY DIFFRACTIONf_dihedral_angle_d17.4116688
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.56-1.580.36631330.33652523X-RAY DIFFRACTION95.44
1.58-1.610.31341310.29722534X-RAY DIFFRACTION99.96
1.61-1.630.31891400.28032649X-RAY DIFFRACTION99.93
1.64-1.660.32341360.26542595X-RAY DIFFRACTION99.93
1.66-1.70.28671410.25322585X-RAY DIFFRACTION99.89
1.7-1.730.27161350.24432598X-RAY DIFFRACTION99.85
1.73-1.770.26571380.23682611X-RAY DIFFRACTION99.78
1.77-1.810.26541390.21492588X-RAY DIFFRACTION99.93
1.81-1.860.30411400.18852584X-RAY DIFFRACTION99.85
1.86-1.910.27261350.18032623X-RAY DIFFRACTION99.96
1.91-1.960.21621390.16922585X-RAY DIFFRACTION99.96
1.96-2.030.23631370.15222630X-RAY DIFFRACTION99.96
2.03-2.10.16731390.15692612X-RAY DIFFRACTION99.71
2.1-2.180.22521380.14582568X-RAY DIFFRACTION99.89
2.18-2.280.21021370.15222588X-RAY DIFFRACTION99.96
2.28-2.40.20361390.14722609X-RAY DIFFRACTION99.93
2.4-2.550.23591360.15042601X-RAY DIFFRACTION100
2.55-2.750.24551330.14852616X-RAY DIFFRACTION100
2.75-3.020.19661420.15262603X-RAY DIFFRACTION99.93
3.03-3.460.20751390.14382608X-RAY DIFFRACTION100
3.46-4.360.17591340.14022585X-RAY DIFFRACTION99.96
4.36-42.190.21831380.17832613X-RAY DIFFRACTION99.96

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbjlvh1.pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more