[English] 日本語
Yorodumi
- PDB-7seo: Crystal Structure of Caspase-3 with Peptide Inhibitor Ac-VDV(DAB)D-CHO -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7seo
TitleCrystal Structure of Caspase-3 with Peptide Inhibitor Ac-VDV(DAB)D-CHO
Components
  • ACE-VAL-ASP-VAL-DAB-ASP
  • Caspase-3 subunit p12
  • Caspase-3 subunit p17
KeywordsAPOPTOSIS / protease / inhibitor / covalent
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 / cellular response to staurosporine / death-inducing signaling complex / cyclin-dependent protein serine/threonine kinase inhibitor activity / Apoptosis induced DNA fragmentation / Apoptotic cleavage of cell adhesion proteins / Caspase activation via Dependence Receptors in the absence of ligand / SMAC, XIAP-regulated apoptotic response / Activation of caspases through apoptosome-mediated cleavage / death receptor binding / Signaling by Hippo / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / axonal fasciculation / regulation of synaptic vesicle cycle / fibroblast apoptotic process / epithelial cell apoptotic process / platelet formation / negative regulation of cytokine production / Other interleukin signaling / positive regulation of amyloid-beta formation / execution phase of apoptosis / negative regulation of B cell proliferation / Apoptotic cleavage of cellular proteins / pyroptotic inflammatory response / negative regulation of activated T cell proliferation / T cell homeostasis / neurotrophin TRK receptor signaling pathway / B cell homeostasis / negative regulation of cell cycle / response to tumor necrosis factor / response to X-ray / cell fate commitment / response to amino acid / Pyroptosis / regulation of macroautophagy / Caspase-mediated cleavage of cytoskeletal proteins / protein maturation / response to glucose / response to glucocorticoid / response to UV / keratinocyte differentiation / striated muscle cell differentiation / Degradation of the extracellular matrix / enzyme activator activity / intrinsic apoptotic signaling pathway / erythrocyte differentiation / hippocampus development / response to nicotine / apoptotic signaling pathway / sensory perception of sound / protein catabolic process / regulation of protein stability / protein processing / response to hydrogen peroxide / neuron differentiation / response to wounding / positive regulation of neuron apoptotic process / response to estradiol / peptidase activity / heart development / protease binding / neuron apoptotic process / response to lipopolysaccharide / aspartic-type endopeptidase activity / learning or memory / response to hypoxia / postsynaptic density / response to xenobiotic stimulus / cysteine-type endopeptidase activity / neuronal cell body / apoptotic process / DNA damage response / protein-containing complex binding / glutamatergic synapse / proteolysis / nucleoplasm / nucleus / cytosol / cytoplasm
Similarity search - Function
Peptidase C14 family / 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 ...Peptidase C14 family / 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
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.25 Å
AuthorsFuller, J.L. / Finzel, B.C.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)1R01AG062199-0 United States
CitationJournal: Acs Pharmacol Transl Sci / Year: 2022
Title: Structure-Based Design and Biological Evaluation of Novel Caspase-2 Inhibitors Based on the Peptide AcVDVAD-CHO and the Caspase-2-Mediated Tau Cleavage Sequence YKPVD314.
Authors: Bresinsky, M. / Strasser, J.M. / Vallaster, B. / Liu, P. / McCue, W.M. / Fuller, J. / Hubmann, A. / Singh, G. / Nelson, K.M. / Cuellar, M.E. / Wilmot, C.M. / Finzel, B.C. / Ashe, K.H. / ...Authors: Bresinsky, M. / Strasser, J.M. / Vallaster, B. / Liu, P. / McCue, W.M. / Fuller, J. / Hubmann, A. / Singh, G. / Nelson, K.M. / Cuellar, M.E. / Wilmot, C.M. / Finzel, B.C. / Ashe, K.H. / Walters, M.A. / Pockes, S.
History
DepositionSep 30, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 5, 2022Provider: repository / Type: Initial release
Revision 1.1Feb 9, 2022Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.3Oct 30, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Caspase-3 subunit p17
B: Caspase-3 subunit p12
C: Caspase-3 subunit p17
D: Caspase-3 subunit p12
F: ACE-VAL-ASP-VAL-DAB-ASP
G: ACE-VAL-ASP-VAL-DAB-ASP


Theoretical massNumber of molelcules
Total (without water)56,7116
Polymers56,7116
Non-polymers00
Water1,06359
1
A: Caspase-3 subunit p17
B: Caspase-3 subunit p12
F: ACE-VAL-ASP-VAL-DAB-ASP


Theoretical massNumber of molelcules
Total (without water)28,3553
Polymers28,3553
Non-polymers00
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5640 Å2
ΔGint-33 kcal/mol
Surface area11020 Å2
MethodPISA
2
C: Caspase-3 subunit p17
D: Caspase-3 subunit p12
G: ACE-VAL-ASP-VAL-DAB-ASP


Theoretical massNumber of molelcules
Total (without water)28,3553
Polymers28,3553
Non-polymers00
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5410 Å2
ΔGint-33 kcal/mol
Surface area11000 Å2
MethodPISA
Unit cell
Length a, b, c (Å)50.464, 66.127, 83.468
Angle α, β, γ (deg.)90.000, 90.870, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Caspase-3 subunit p17


Mass: 16524.814 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CASP3, CPP32 / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta 2 PLysS / References: UniProt: P42574
#2: Protein Caspase-3 subunit p12


Mass: 11257.953 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CASP3, CPP32 / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta 2 PLysS / References: UniProt: P42574
#3: Protein/peptide ACE-VAL-ASP-VAL-DAB-ASP


Mass: 572.609 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 59 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.46 Å3/Da / Density % sol: 49.91 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.3
Details: 15% PEG 6000, 5% Glycerol, 100mM Sodium Citrate (pH 5.3), 10mM DTT, 3mM NaN3

-
Data collection

DiffractionMean temperature: 80 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS EIGER2 X 9M / Detector: PIXEL / Date: Jul 17, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3.25→83.46 Å / Num. obs: 8215 / % possible obs: 93.4 % / Redundancy: 2.3 % / Biso Wilson estimate: 48.01 Å2 / CC1/2: 0.99 / Rmerge(I) obs: 0.096 / Rpim(I) all: 0.074 / Rrim(I) all: 0.122 / Net I/σ(I): 5.2 / Num. measured all: 19027 / Scaling rejects: 14
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
3.25-3.432.20.207235910760.9420.1560.2613.384.3
10.28-83.462.30.0356382820.9970.0280.0458.894.9

-
Processing

Software
NameVersionClassification
PHENIX1.19.2_4158refinement
Aimless0.7.4data scaling
PDB_EXTRACT3.27data extraction
autoPROCdata reduction
REFMACphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2H65

2h65


Resolution: 3.25→19.9 Å / SU ML: 0.31 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 25.82 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2632 433 5.32 %
Rwork0.189 7712 -
obs0.1928 8145 92.87 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 109.38 Å2 / Biso mean: 48.5047 Å2 / Biso min: 10.86 Å2
Refinement stepCycle: final / Resolution: 3.25→19.9 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3872 0 0 59 3931
Biso mean---37.68 -
Num. residues----480
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 3

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
3.25-3.720.2741610.18342419258089
3.72-4.670.27511410.17622590273194
4.67-19.90.24581310.20332703283496

+
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