[English] 日本語
Yorodumi
- PDB-6u6f: The crystal structure of anti-apoptotic Mcl-1 protein in complex ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6u6f
TitleThe crystal structure of anti-apoptotic Mcl-1 protein in complex with 2, 5-substituted benzoic acid inhibitor 21
ComponentsInduced myeloid leukemia cell differentiation protein Mcl-1
KeywordsAPOPTOSIS/INHIBITOR / Apoptosis / Mcl1 / Bfl1/A1 / protein-protein interaction / BH3 mimetics / cancer / APOPTOSIS-INHIBITOR complex
Function / homology
Function and homology information


positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / cell fate determination / cellular homeostasis / BH domain binding / mitochondrial fusion / Bcl-2 family protein complex / BH3 domain binding / negative regulation of anoikis / protein transmembrane transporter activity / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand ...positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / cell fate determination / cellular homeostasis / BH domain binding / mitochondrial fusion / Bcl-2 family protein complex / BH3 domain binding / negative regulation of anoikis / protein transmembrane transporter activity / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / extrinsic apoptotic signaling pathway in absence of ligand / negative regulation of autophagy / response to cytokine / release of cytochrome c from mitochondria / intrinsic apoptotic signaling pathway in response to DNA damage / Signaling by ALK fusions and activated point mutants / channel activity / regulation of apoptotic process / Interleukin-4 and Interleukin-13 signaling / mitochondrial outer membrane / positive regulation of apoptotic process / protein heterodimerization activity / DNA damage response / negative regulation of apoptotic process / mitochondrion / nucleoplasm / nucleus / membrane / cytosol / cytoplasm
Similarity search - Function
Apoptosis regulator, Mcl-1 / Blc2-like / Apoptosis Regulator Bcl-x / 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-2 family ...Apoptosis regulator, Mcl-1 / Blc2-like / Apoptosis Regulator Bcl-x / 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-2 family / BCL (B-Cell lymphoma); contains BH1, BH2 regions / Bcl2-like / Bcl-2, Bcl-2 homology region 1-3 / Apoptosis regulator proteins, Bcl-2 family / BCL2-like apoptosis inhibitors family profile. / Bcl-2-like superfamily / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-PZY / Induced myeloid leukemia cell differentiation protein Mcl-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.9 Å
AuthorsYang, Y. / Stuckey, J.A. / Nikolovska-Coleska, Z.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01 CA-149442 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)R21 NS056915 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)P30 CA046592 United States
CitationJournal: J.Med.Chem. / Year: 2020
Title: Discovery and Characterization of 2,5-Substituted Benzoic Acid Dual Inhibitors of the Anti-apoptotic Mcl-1 and Bfl-1 Proteins.
Authors: Kump, K.J. / Miao, L. / Mady, A.S.A. / Ansari, N.H. / Shrestha, U.K. / Yang, Y. / Pal, M. / Liao, C. / Perdih, A. / Abulwerdi, F.A. / Chinnaswamy, K. / Meagher, J.L. / Carlson, J.M. / ...Authors: Kump, K.J. / Miao, L. / Mady, A.S.A. / Ansari, N.H. / Shrestha, U.K. / Yang, Y. / Pal, M. / Liao, C. / Perdih, A. / Abulwerdi, F.A. / Chinnaswamy, K. / Meagher, J.L. / Carlson, J.M. / Khanna, M. / Stuckey, J.A. / Nikolovska-Coleska, Z.
History
DepositionAug 29, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 4, 2020Provider: repository / Type: Initial release
Revision 1.1Mar 25, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
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: Induced myeloid leukemia cell differentiation protein Mcl-1
C: Induced myeloid leukemia cell differentiation protein Mcl-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,7867
Polymers53,5153
Non-polymers2,2714
Water93752
1
A: Induced myeloid leukemia cell differentiation protein Mcl-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,9743
Polymers17,8381
Non-polymers1,1362
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Induced myeloid leukemia cell differentiation protein Mcl-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,4062
Polymers17,8381
Non-polymers5681
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: Induced myeloid leukemia cell differentiation protein Mcl-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,4062
Polymers17,8381
Non-polymers5681
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)68.450, 68.450, 363.650
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number178
Space group name H-MP6122

-
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: 17838.229 Da / Num. of mol.: 3
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: Chemical
ChemComp-PZY / 2-[({4-[(4-tert-butylphenyl)methyl]piperazin-1-yl}sulfonyl)amino]-5-[(2-phenylethyl)sulfanyl]benzoic acid


Mass: 567.762 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C30H37N3O4S2 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 52 / 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: 2.3 Å3/Da / Density % sol: 46.47 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: PEG3350 20-22.5%, 0.1 M Bis-Tris 6.5, 0.28 M Ammonium acetate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-G / Wavelength: 0.97856 Å
DetectorType: MARRESEARCH / Detector: CCD / Date: Aug 15, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97856 Å / Relative weight: 1
ReflectionResolution: 2.9→200 Å / Num. obs: 12245 / % possible obs: 99.9 % / Redundancy: 18 % / Biso Wilson estimate: 71.33 Å2 / Rmerge(I) obs: 0.12 / Rpim(I) all: 0.028 / Rrim(I) all: 0.124 / Χ2: 1.095 / Net I/σ(I): 6.6 / Num. measured all: 220047
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
2.9-2.9516.80.7065820.9270.170.7270.695100
2.95-316.90.5315840.960.1280.5480.736100
3-3.0616.90.4495830.9830.1080.4620.761100
3.06-3.1216.20.4136130.9750.10.4260.805100
3.12-3.1917.40.3585690.9790.0860.3690.885100
3.19-3.2716.80.3146000.9830.0760.3240.865100
3.27-3.35170.2885740.9870.070.2970.927100
3.35-3.4416.80.2536050.9830.0610.2611.029100
3.44-3.5417.20.2025870.9930.0490.2081.089100
3.54-3.6517.10.1695890.9960.0410.1741.118100
3.65-3.78170.1366220.9960.0330.141.174100
3.78-3.9417.20.1255900.9950.030.1281.243100
3.94-4.1217.50.116060.9970.0260.1131.136100
4.12-4.3317.60.16090.9980.0240.1031.279100
4.33-4.618.50.0996160.9980.0240.1021.359100
4.6-4.9619.10.1026230.9960.0240.1051.305100
4.96-5.4620.10.0916200.9980.0210.0941.296100
5.46-6.2521.20.0886540.9980.0190.091.206100
6.25-7.8721.60.0736590.9980.0160.0751.283100
7.87-20019.20.0557600.9990.0120.0561.29898.6

-
Processing

Software
NameVersionClassification
HKL-2000data scaling
BUSTER2.10.3refinement
PDB_EXTRACT3.25data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2PQK

2pqk


Resolution: 2.9→36.07 Å / Cor.coef. Fo:Fc: 0.909 / Cor.coef. Fo:Fc free: 0.861 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.457
RfactorNum. reflection% reflectionSelection details
Rfree0.279 590 4.87 %RANDOM
Rwork0.238 ---
obs0.24 12127 99.9 %-
Displacement parametersBiso max: 125.44 Å2 / Biso mean: 52.78 Å2 / Biso min: 24.15 Å2
Baniso -1Baniso -2Baniso -3
1--3.6051 Å20 Å20 Å2
2---3.6051 Å20 Å2
3---7.2102 Å2
Refine analyzeLuzzati coordinate error obs: 0.45 Å
Refinement stepCycle: final / Resolution: 2.9→36.07 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3494 0 140 52 3686
Biso mean--50.8 41.79 -
Num. residues----456
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1288SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes630HARMONIC5
X-RAY DIFFRACTIONt_it3704HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion477SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact4382SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d3704HARMONIC20.008
X-RAY DIFFRACTIONt_angle_deg5022HARMONIC20.89
X-RAY DIFFRACTIONt_omega_torsion1.74
X-RAY DIFFRACTIONt_other_torsion19.13
LS refinement shellResolution: 2.9→2.94 Å / Rfactor Rfree error: 0 / Total num. of bins used: 29
RfactorNum. reflection% reflection
Rfree0.3118 12 2.86 %
Rwork0.291 407 -
all0.2917 419 -
obs--100 %

+
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