[English] 日本語
Yorodumi
- PDB-6vbx: Crystal structure of Mcl-1 in complex with 138E12 peptide, Lys-co... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6vbx
TitleCrystal structure of Mcl-1 in complex with 138E12 peptide, Lys-covalent antagonist
Components
  • Induced myeloid leukemia cell differentiation protein Mcl-1
  • Synthetic peptidePeptide synthesis
KeywordsAPOPTOSIS / MCL-1 / 138E12 peptide / Lys-covalent antagonists
Function / homology
Function and homology information


BIM-BCL-xl complex / BIM-BCL-2 complex / regulation of developmental pigmentation / RUNX3 regulates BCL2L11 (BIM) transcription / positive regulation of mitochondrial membrane permeability involved in apoptotic process / developmental pigmentation / Activation of BIM and translocation to mitochondria / positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / positive regulation of fibroblast apoptotic process / apoptotic process involved in embryonic digit morphogenesis ...BIM-BCL-xl complex / BIM-BCL-2 complex / regulation of developmental pigmentation / RUNX3 regulates BCL2L11 (BIM) transcription / positive regulation of mitochondrial membrane permeability involved in apoptotic process / developmental pigmentation / Activation of BIM and translocation to mitochondria / positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / positive regulation of fibroblast apoptotic process / apoptotic process involved in embryonic digit morphogenesis / ear development / tube formation / meiosis I / positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / cellular homeostasis / mammary gland development / cell fate determination / BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members / positive regulation of T cell apoptotic process / regulation of organ growth / cellular response to glucocorticoid stimulus / channel activity / mitochondrial fusion / Bcl-2 family protein complex / myeloid cell homeostasis / FOXO-mediated transcription of cell death genes / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / NRAGE signals death through JNK / thymocyte apoptotic process / T cell homeostasis / BH3 domain binding / odontogenesis of dentin-containing tooth / positive regulation of IRE1-mediated unfolded protein response / positive regulation of release of cytochrome c from mitochondria / B cell homeostasis / protein transmembrane transporter activity / negative regulation of anoikis / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / endomembrane system / positive regulation of cell cycle / positive regulation of intrinsic apoptotic signaling pathway / extrinsic apoptotic signaling pathway in absence of ligand / spleen development / FLT3 Signaling / response to endoplasmic reticulum stress / negative regulation of autophagy / cell-matrix adhesion / post-embryonic development / release of cytochrome c from mitochondria / thymus development / kidney development / response to cytokine / positive regulation of protein-containing complex assembly / male gonad development / activation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of neuron apoptotic process / intrinsic apoptotic signaling pathway in response to DNA damage / Signaling by BRAF and RAF1 fusions / microtubule binding / spermatogenesis / Interleukin-4 and Interleukin-13 signaling / regulation of apoptotic process / in utero embryonic development / mitochondrial outer membrane / molecular adaptor activity / positive regulation of apoptotic process / protein heterodimerization activity / apoptotic process / DNA damage response / negative regulation of apoptotic process / protein kinase binding / protein homodimerization activity / mitochondrion / nucleoplasm / membrane / nucleus / cytosol / cytoplasm
Similarity search - Function
Apoptosis, Bim N-terminal / Bcl-2-like protein 11 / Bim protein N-terminus / Bcl-x interacting, BH3 domain / Bcl-x interacting, BH3 domain / Apoptosis regulator, Mcl-1 / Apoptosis regulator, Bcl-2, BH3 motif, conserved site / Apoptosis regulator, Bcl-2 family BH3 motif signature. / Apoptosis regulator, Bcl-2, BH1 motif, conserved site / Apoptosis regulator, Bcl-2 family BH1 motif signature. ...Apoptosis, Bim N-terminal / Bcl-2-like protein 11 / Bim protein N-terminus / Bcl-x interacting, BH3 domain / Bcl-x interacting, BH3 domain / Apoptosis regulator, Mcl-1 / Apoptosis regulator, Bcl-2, BH3 motif, conserved site / Apoptosis regulator, Bcl-2 family BH3 motif signature. / Apoptosis regulator, Bcl-2, BH1 motif, conserved site / Apoptosis regulator, Bcl-2 family BH1 motif signature. / Apoptosis regulator, Bcl-2, BH2 motif, conserved site / Apoptosis regulator, Bcl-2 family BH2 motif signature. / BCL (B-Cell lymphoma); contains BH1, BH2 regions / Bcl-2 family / Bcl-2, Bcl-2 homology region 1-3 / Bcl2-like / Apoptosis regulator proteins, Bcl-2 family / BCL2-like apoptosis inhibitors family profile. / Bcl-2-like superfamily
Similarity search - Domain/homology
Bcl-2-like protein 11 / Induced myeloid leukemia cell differentiation protein Mcl-1
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.95 Å
AuthorsPellecchia, M. / Perry, J.J. / Kenjic, N. / Assar, Z.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)CA168517 United States
Citation
Journal: J.Med.Chem. / Year: 2021
Title: Design, Synthesis, and Structural Characterization of Lysine Covalent BH3 Peptides Targeting Mcl-1.
Authors: Gambini, L. / Udompholkul, P. / Baggio, C. / Muralidharan, A. / Kenjic, N. / Assar, Z. / Perry, J.J.P. / Pellecchia, M.
#1: Journal: Meth. Enzymol. / Year: 1997
Title: Processing of X-ray diffraction data collected in oscillation mode.
Authors: Otwinowski, Z. / Minor, W.
#2: Journal: J Appl Crystallogr / Year: 2007
Title: Phaser crystallographic software.
Authors: McCoy, A.J. / Grosse-Kunstleve, R.W. / Adams, P.D. / Winn, M.D. / Storoni, L.C. / Read, R.J.
#3: Journal: Acta Crystallogr. D Biol. Crystallogr. / Year: 2004
Title: REFMAC5 dictionary: organization of prior chemical knowledge and guidelines for its use.
Authors: Vagin, A.A. / Steiner, R.A. / Lebedev, A.A. / Potterton, L. / McNicholas, S. / Long, F. / Murshudov, G.N.
#4: Journal: Acta Crystallogr D Biol Crystallogr / Year: 2004
Title: Coot: model-building tools for molecular graphics.
Authors: Paul Emsley / Kevin Cowtan /
Abstract: CCP4mg is a project that aims to provide a general-purpose tool for structural biologists, providing tools for X-ray structure solution, structure comparison and analysis, and publication-quality ...CCP4mg is a project that aims to provide a general-purpose tool for structural biologists, providing tools for X-ray structure solution, structure comparison and analysis, and publication-quality graphics. The map-fitting tools are available as a stand-alone package, distributed as 'Coot'.
History
DepositionDec 19, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 30, 2020Provider: repository / Type: Initial release
Revision 1.1Jun 9, 2021Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _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 11, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Induced myeloid leukemia cell differentiation protein Mcl-1
B: Synthetic peptide


Theoretical massNumber of molelcules
Total (without water)19,6552
Polymers19,6552
Non-polymers00
Water79344
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1460 Å2
ΔGint-11 kcal/mol
Surface area8440 Å2
MethodPISA
2
A: Induced myeloid leukemia cell differentiation protein Mcl-1
B: Synthetic peptide

A: Induced myeloid leukemia cell differentiation protein Mcl-1
B: Synthetic peptide


Theoretical massNumber of molelcules
Total (without water)39,3114
Polymers39,3114
Non-polymers00
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation4_555y,x,-z1
Buried area4700 Å2
ΔGint-23 kcal/mol
Surface area15100 Å2
MethodPISA
Unit cell
Length a, b, c (Å)54.607, 54.607, 97.838
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number154
Space group name H-MP3221
Space group name HallP322"

-
Components

#1: Protein Induced myeloid leukemia cell differentiation protein Mcl-1 / Bcl-2-like protein 3 / Bcl2-L-3 / Bcl-2-related protein EAT/mcl1 / mcl1/EAT


Mass: 17850.330 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MCL1, BCL2L3 / Production host: Escherichia coli (E. coli) / References: UniProt: Q07820
#2: Protein/peptide Synthetic peptide / Peptide synthesis


Mass: 1805.020 Da / Num. of mol.: 1 / Source method: obtained synthetically
Details: This is a chemically synthesized peptide with unnatural ligand (see ligand section) on the N-terminal end. Ligands is covalently attached to Lys234 of chain A.
Source: (synth.) synthetic construct (others) / References: UniProt: O43521*PLUS
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 44 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.18 Å3/Da / Density % sol: 43.55 %
Crystal growTemperature: 298 K / Method: vapor diffusion, sitting drop
Details: 0.5M Potassium Thiocyanate, 0.1M Sodium Acetate:HCL pH4.6

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 1.127 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Oct 31, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.127 Å / Relative weight: 1
ReflectionResolution: 1.95→34.001 Å / Num. obs: 12721 / % possible obs: 99.75 % / Redundancy: 7.9 % / Biso Wilson estimate: 32.63 Å2 / Rmerge(I) obs: 0.073 / Net I/σ(I): 22
Reflection shellResolution: 1.955→2.025 Å / Redundancy: 8.4 % / Rmerge(I) obs: 0.276 / Mean I/σ(I) obs: 2.3 / Num. unique obs: 1235 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.16_3549refinement
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
Cootmodel building
PDB_EXTRACT3.25data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2NL9

2nl9


Resolution: 1.95→34 Å / SU ML: 0.2912 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 34.0423
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2779 601 4.72 %
Rwork0.2503 12120 -
obs0.2518 12721 99.78 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 35.58 Å2
Refinement stepCycle: LAST / Resolution: 1.95→34 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1234 0 21 44 1299
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00671273
X-RAY DIFFRACTIONf_angle_d0.80691708
X-RAY DIFFRACTIONf_chiral_restr0.0536189
X-RAY DIFFRACTIONf_plane_restr0.004217
X-RAY DIFFRACTIONf_dihedral_angle_d10.0004753
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.95-2.150.35431340.27422992X-RAY DIFFRACTION100
2.15-2.460.32821320.27352965X-RAY DIFFRACTION99.2
2.46-3.10.31211340.26933038X-RAY DIFFRACTION99.97

+
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