[English] 日本語
Yorodumi
- PDB-2h65: Crystal strusture of caspase-3 with inhibitor Ac-VDVAD-Cho -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2h65
TitleCrystal strusture of caspase-3 with inhibitor Ac-VDVAD-Cho
Components
  • Ac-VDVAD-Cho
  • caspase-3, p12 subunit
  • caspase-3, p17 subunit
KeywordsHYDROLASE/HYDROLASE INHIBITOR / ENZYME CATALYSIS / CYSTEINE PROTEASE / APOPTOSIS / INDUCED FIT / HYDROLASE-HYDROLASE INHIBITOR COMPLEX
Function / homology
Function and homology information


caspase-3 / Stimulation of the cell death response by PAK-2p34 / phospholipase A2 activator activity / anterior neural tube closure / intrinsic apoptotic signaling pathway in response to osmotic stress / leukocyte apoptotic process / positive regulation of pyroptotic inflammatory response / glial cell apoptotic process / NADE modulates death signalling / luteolysis ...caspase-3 / Stimulation of the cell death response by PAK-2p34 / phospholipase A2 activator activity / anterior neural tube closure / intrinsic apoptotic signaling pathway in response to osmotic stress / leukocyte apoptotic process / positive regulation of pyroptotic inflammatory response / glial cell apoptotic process / NADE modulates death signalling / luteolysis / response to cobalt ion / cysteine-type endopeptidase activity involved in apoptotic signaling pathway / death-inducing signaling complex / cyclin-dependent protein serine/threonine kinase inhibitor activity / cellular response to staurosporine / Apoptosis induced DNA fragmentation / Apoptotic cleavage of cell adhesion proteins / cysteine-type endopeptidase activity involved in execution phase of apoptosis / Caspase activation via Dependence Receptors in the absence of ligand / death receptor binding / SMAC, XIAP-regulated apoptotic response / axonal fasciculation / Activation of caspases through apoptosome-mediated cleavage / Signaling by Hippo / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / cysteine-type endopeptidase activity involved in apoptotic process / fibroblast apoptotic process / execution phase of apoptosis / negative regulation of cytokine production / epithelial cell apoptotic process / platelet formation / Other interleukin signaling / positive regulation of amyloid-beta formation / pyroptotic inflammatory response / Apoptotic cleavage of cellular proteins / negative regulation of B cell proliferation / T cell homeostasis / negative regulation of activated T cell proliferation / neurotrophin TRK receptor signaling pathway / B cell homeostasis / protein maturation / negative regulation of cell cycle / response to X-ray / Caspase-mediated cleavage of cytoskeletal proteins / regulation of macroautophagy / response to amino acid / cell fate commitment / Pyroptosis / response to tumor necrosis factor / response to glucose / response to UV / response to glucocorticoid / keratinocyte differentiation / striated muscle cell differentiation / Degradation of the extracellular matrix / intrinsic apoptotic signaling pathway / erythrocyte differentiation / response to nicotine / apoptotic signaling pathway / hippocampus development / sensory perception of sound / protein catabolic process / regulation of protein stability / response to hydrogen peroxide / protein processing / neuron differentiation / response to wounding / positive regulation of neuron apoptotic process / response to estradiol / heart development / peptidase activity / neuron apoptotic process / protease binding / response to lipopolysaccharide / aspartic-type endopeptidase activity / response to hypoxia / learning or memory / response to xenobiotic stimulus / positive regulation of apoptotic process / cysteine-type endopeptidase activity / neuronal cell body / apoptotic process / DNA damage response / protein-containing complex binding / proteolysis / nucleoplasm / nucleus / cytosol / cytoplasm
Similarity search - Function
Caspase-like / 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 ...Caspase-like / 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 / Alpha-Beta Plaits / Rossmann fold / 2-Layer Sandwich / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Caspase-2 Inhibitor; Ac-VDVAD-Cho / Caspase-3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsFang, B. / Boross, P.I. / Tozser, J. / Weber, I.T.
CitationJournal: J.Mol.Biol. / Year: 2006
Title: Structural and kinetic analysis of caspase-3 reveals role for s5 binding site in substrate recognition
Authors: Fang, B. / Boross, P.I. / Tozser, J. / Weber, I.T.
History
DepositionMay 30, 2006Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 19, 2006Provider: repository / Type: Initial release
Revision 1.1May 1, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Atomic model / Database references ...Atomic model / Database references / Derived calculations / Non-polymer description / Structure summary / Version format compliance
Revision 1.3Dec 12, 2012Group: Other
Revision 1.4Aug 30, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_conn / struct_ref_seq_dif
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_ref_seq_dif.details
Revision 1.5Nov 15, 2023Group: Data collection / Category: chem_comp_atom / chem_comp_bond / Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_2

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: caspase-3, p17 subunit
B: caspase-3, p12 subunit
C: caspase-3, p17 subunit
D: caspase-3, p12 subunit
E: Ac-VDVAD-Cho
F: Ac-VDVAD-Cho


Theoretical massNumber of molelcules
Total (without water)56,6256
Polymers56,6256
Non-polymers00
Water1,54986
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area15880 Å2
ΔGint-84 kcal/mol
Surface area17340 Å2
MethodPISA
Unit cell
Length a, b, c (Å)49.890, 67.400, 93.490
Angle α, β, γ (deg.)90.000, 100.800, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein caspase-3, p17 subunit / / E.C.3.4.22.- / CASP-3 / Apopain / Cysteine protease CPP32 / Yama protein / CPP-32 / SREBP cleavage activity 1 / SCA-1


Mass: 16524.814 Da / Num. of mol.: 2 / Fragment: residues 29-174
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CASP3, CPP32 / Plasmid: pET23b / Species (production host): Escherichia coli / Production host: Escherichia coli BL21 (bacteria) / Strain (production host): BL21
References: UniProt: P42574, Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases
#2: Protein caspase-3, p12 subunit / / E.C.3.4.22.-


Mass: 11257.953 Da / Num. of mol.: 2 / Fragment: residues 184-277
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CASP3, CPP32 / Plasmid: pET23b / Species (production host): Escherichia coli / Production host: Escherichia coli BL21 (bacteria) / Strain (production host): BL21
References: UniProt: P42574, Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases
#3: Protein/peptide Ac-VDVAD-Cho


Type: Peptide-like / Class: Inhibitor / Mass: 529.584 Da / Num. of mol.: 2 / Source method: obtained synthetically / References: Caspase-2 Inhibitor; Ac-VDVAD-Cho
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 86 / Source method: isolated from a natural source / Formula: H2O
Compound detailsTHE INHIBITOR IS COVALENTLY CONNECTED TO CYS OF THE ENZYME TO FORM A HEMITHIOKETAL

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.73 Å3/Da / Density % sol: 54.89 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6.5
Details: 100 mM sodium citrate, 5% glycerol, 10 mM dithiothreitol and 14-18% PEG6000, pH 6.5, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Mar 15, 2005
RadiationMonochromator: Si 220 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.2→50 Å / Num. all: 34990 / Num. obs: 34990 / % possible obs: 97.6 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 3.2 % / Biso Wilson estimate: 24.5 Å2 / Rmerge(I) obs: 0.088 / Net I/σ(I): 11
Reflection shellResolution: 2.2→2.3 Å / Redundancy: 2.8 % / Rmerge(I) obs: 0.297 / Mean I/σ(I) obs: 4 / % possible all: 98.1

-
Processing

Software
NameClassification
MADCCDdata collection
HKL-2000data reduction
AMoREphasing
CNSrefinement
MADCCDdata reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1CP3

1cp3


Resolution: 2.3→10 Å / FOM work R set: 0.833 / Isotropic thermal model: Isotropic
Cross valid method: maximum likelihood target using amplitudes
σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.246 1265 4.7 %RANDOM
Rwork0.209 ---
all0.208 25859 --
obs0.198 23763 96 %-
Solvent computationBsol: 40.134 Å2
Displacement parametersBiso mean: 29.896 Å2
Baniso -1Baniso -2Baniso -3
1--2.128 Å20 Å28.156 Å2
2---4.882 Å20 Å2
3---7.01 Å2
Refinement stepCycle: LAST / Resolution: 2.3→10 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3852 0 0 86 3938
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_bond_d0.007
X-RAY DIFFRACTIONc_angle_d1.266
X-RAY DIFFRACTIONc_mcbond_it1.4891.5
X-RAY DIFFRACTIONc_scbond_it2.4932
X-RAY DIFFRACTIONc_mcangle_it2.4852
X-RAY DIFFRACTIONc_scangle_it3.812.5
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 25

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection obs
2.3-2.330.284540.27927981
2.33-2.360.295650.25885950
2.36-2.40.243470.245927974
2.4-2.440.279510.251898949
2.44-2.480.289440.2649701014
2.48-2.520.289510.2539611012
2.52-2.560.276430.2419691012
2.56-2.610.342380.2589791017
2.61-2.660.328470.26951998
2.66-2.720.409460.2679891035
2.72-2.780.313500.249811031
2.78-2.850.312430.2579771020
2.85-2.920.287530.24110391092
2.92-3.010.259450.2249721017
3.01-3.10.268500.20710171067
3.1-3.210.259520.2389981050
3.21-3.330.245470.20510381085
3.33-3.480.201460.1910021048
3.48-3.650.212610.1810051066
3.65-3.870.201590.18210181077
3.87-4.150.206580.17810111069
4.15-4.530.156420.16210261068
4.53-5.110.193500.16910151065
5.11-6.170.291630.21310191082
6.17-100.216600.18510201080
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1protein_rep.paramprotein.top
X-RAY DIFFRACTION2CNS_TOPPAR:water_rep.paramCNS_TOPPAR:water.top

+
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://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