[English] 日本語
Yorodumi
- PDB-4nbk: Tailoring Small Molecules for an Allosteric Site on Procaspase-6 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4nbk
TitleTailoring Small Molecules for an Allosteric Site on Procaspase-6
ComponentsCaspase-6
Keywordshydrolase/hydrolase inhibitor / procaspse-6 / caspase-6 zymogen / allosteric / Structure Based Drug Design / Cysteine protease / hydrolase-hydrolase inhibitor complex
Function / homology
Function and homology information


caspase-6 / Breakdown of the nuclear lamina / regulation of programmed cell death / positive regulation of necroptotic process / cellular response to staurosporine / cysteine-type endopeptidase activity involved in execution phase of apoptosis / cysteine-type endopeptidase activity involved in apoptotic process / hepatocyte apoptotic process / TP53 Regulates Transcription of Caspase Activators and Caspases / Apoptotic cleavage of cellular proteins ...caspase-6 / Breakdown of the nuclear lamina / regulation of programmed cell death / positive regulation of necroptotic process / cellular response to staurosporine / cysteine-type endopeptidase activity involved in execution phase of apoptosis / cysteine-type endopeptidase activity involved in apoptotic process / hepatocyte apoptotic process / TP53 Regulates Transcription of Caspase Activators and Caspases / Apoptotic cleavage of cellular proteins / pyroptotic inflammatory response / protein autoprocessing / intrinsic apoptotic signaling pathway by p53 class mediator / Caspase-mediated cleavage of cytoskeletal proteins / cysteine-type peptidase activity / epithelial cell differentiation / activation of innate immune response / positive regulation of neuron apoptotic process / positive regulation of apoptotic process / cysteine-type endopeptidase activity / apoptotic process / proteolysis / nucleoplasm / identical protein binding / nucleus / cytoplasm / cytosol
Similarity search - Function
Rossmann fold - #1460 / Peptidase family C14A, His active site / Caspase family histidine active site. / Peptidase C14, caspase non-catalytic subunit p10 / Peptidase family C14A, cysteine active site / Caspase family cysteine active site. / Caspase family p10 domain profile. / Peptidase C14A, caspase catalytic domain / Caspase, interleukin-1 beta converting enzyme (ICE) homologues / Peptidase C14, p20 domain ...Rossmann fold - #1460 / Peptidase family C14A, His active site / Caspase family histidine active site. / Peptidase C14, caspase non-catalytic subunit p10 / Peptidase family C14A, cysteine active site / Caspase family cysteine active site. / Caspase family p10 domain profile. / Peptidase C14A, caspase catalytic domain / Caspase, interleukin-1 beta converting enzyme (ICE) homologues / Peptidase C14, p20 domain / Caspase family p20 domain profile. / : / Caspase domain / Caspase-like domain superfamily / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
2-{[(3-methylpyridin-2-yl)amino]methyl}phenol / PHOSPHATE ION / Caspase-6
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.936 Å
AuthorsMurray, J.M. / Steffek, M.
CitationJournal: Chemmedchem / Year: 2014
Title: Tailoring small molecules for an allosteric site on procaspase-6.
Authors: Murray, J. / Giannetti, A.M. / Steffek, M. / Gibbons, P. / Hearn, B.R. / Cohen, F. / Tam, C. / Pozniak, C. / Bravo, B. / Lewcock, J. / Jaishankar, P. / Ly, C.Q. / Zhao, X. / Tang, Y. / ...Authors: Murray, J. / Giannetti, A.M. / Steffek, M. / Gibbons, P. / Hearn, B.R. / Cohen, F. / Tam, C. / Pozniak, C. / Bravo, B. / Lewcock, J. / Jaishankar, P. / Ly, C.Q. / Zhao, X. / Tang, Y. / Chugha, P. / Arkin, M.R. / Flygare, J. / Renslo, A.R.
History
DepositionOct 23, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 1, 2014Provider: repository / Type: Initial release
Revision 1.1Jan 22, 2014Group: Database references
Revision 1.2Feb 28, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Caspase-6
B: Caspase-6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)65,4129
Polymers64,6282
Non-polymers7847
Water5,765320
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4710 Å2
ΔGint-56 kcal/mol
Surface area20510 Å2
MethodPISA
Unit cell
Length a, b, c (Å)115.700, 115.700, 79.691
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number96
Space group name H-MP43212
Components on special symmetry positions
IDModelComponents
11A-619-

HOH

21A-629-

HOH

31B-578-

HOH

-
Components

#1: Protein Caspase-6 / CASP-6 / Apoptotic protease Mch-2 / Caspase-6 subunit p18 / Caspase-6 subunit p11


Mass: 32313.857 Da / Num. of mol.: 2 / Fragment: unp residues 24-293 / Mutation: C163A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CASP6, MCH2, procaspase-6 / Plasmid: pET / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 (DE3) / References: UniProt: P55212, caspase-6
#2: Chemical ChemComp-2J5 / 2-{[(3-methylpyridin-2-yl)amino]methyl}phenol


Mass: 214.263 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C13H14N2O
#3: Chemical
ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: PO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 320 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.06 Å3/Da / Density % sol: 40.39 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 8.5
Details: 2-Methyl-2,4-pentanediol, 0.3 M Ammonium Phosphate monobasic, 0.1 M Tris, pH 8.5, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 0.97946 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Jan 26, 2010
RadiationProtocol: SINGLE / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97946 Å / Relative weight: 1
ReflectionResolution: 1.936→115.742 Å / Num. all: 40739 / Num. obs: 40739 / % possible obs: 100 % / Redundancy: 7.1 % / Rsym value: 0.084 / Net I/σ(I): 15.7
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsRsym valueDiffraction-ID% possible all
1.94-2.046.60.5011.60.5011100
2.04-2.1670.3352.30.3351100
2.16-2.317.20.2343.30.2341100
2.31-2.57.40.1764.50.1761100
2.5-2.747.40.1296.10.1291100
2.74-3.067.40.08690.0861100
3.06-3.537.30.05713.10.0571100
3.53-4.337.20.041170.041199.9
4.33-6.1270.03816.30.038199.7
6.12-115.7426.40.03316.20.033199.8

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
SCALA3.3.20data scaling
PHASERphasing
PHENIX1.8.4_1492refinement
PDB_EXTRACT3.11data extraction
CBASSdata collection
XSCALEdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.936→65.63 Å / Occupancy max: 1 / Occupancy min: 0.39 / SU ML: 0.18 / σ(F): 1.35 / Phase error: 16.45 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1884 2089 5.13 %
Rwork0.1604 --
obs0.1618 40682 99.61 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 26.9136 Å2
Refinement stepCycle: LAST / Resolution: 1.936→65.63 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3988 0 46 320 4354
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0064154
X-RAY DIFFRACTIONf_angle_d0.9925606
X-RAY DIFFRACTIONf_dihedral_angle_d13.2511522
X-RAY DIFFRACTIONf_chiral_restr0.045597
X-RAY DIFFRACTIONf_plane_restr0.005739
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.9356-1.98060.29651290.22352423X-RAY DIFFRACTION96
1.9806-2.03020.20951440.19092525X-RAY DIFFRACTION100
2.0302-2.08510.21541330.17812537X-RAY DIFFRACTION100
2.0851-2.14640.18771270.1692561X-RAY DIFFRACTION100
2.1464-2.21570.20021470.15912553X-RAY DIFFRACTION100
2.2157-2.29490.21121440.1622522X-RAY DIFFRACTION100
2.2949-2.38680.22621360.16052551X-RAY DIFFRACTION100
2.3868-2.49540.19751560.15812561X-RAY DIFFRACTION100
2.4954-2.6270.19181280.1632572X-RAY DIFFRACTION100
2.627-2.79160.19361380.17122564X-RAY DIFFRACTION100
2.7916-3.00710.18391560.15992566X-RAY DIFFRACTION100
3.0071-3.30970.1871460.15782597X-RAY DIFFRACTION100
3.3097-3.78860.17511420.14382619X-RAY DIFFRACTION100
3.7886-4.7730.15541320.13252638X-RAY DIFFRACTION100
4.773-65.66740.17581310.17792804X-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)
11.7048-0.2555-0.27261.37040.25721.2703-0.0282-0.0684-0.14410.0365-0.0163-0.00650.11320.02460.03490.13490.01160.01110.13770.03580.136123.320217.41619.3049
21.7366-0.04260.01911.6835-0.12531.56330.0634-0.06920.23610.0699-0.0691-0.0184-0.19610.03870.02840.1794-0.00550.00210.0919-0.01570.164426.351844.251214.6143
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain A
2X-RAY DIFFRACTION2chain B

+
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