[English] 日本語
Yorodumi
- PDB-6fs1: MCL1 in complex with an indole acid ligand -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6fs1
TitleMCL1 in complex with an indole acid ligand
ComponentsInduced myeloid leukemia cell differentiation protein Mcl-1
KeywordsIMMUNE SYSTEM / Mcl1 / indole acid
Function / homology
Function and homology information


positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / cellular homeostasis / cell fate determination / mitochondrial fusion / channel activity / 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 / cellular homeostasis / cell fate determination / mitochondrial fusion / channel activity / 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 / release of cytochrome c from mitochondria / response to cytokine / Signaling by ALK fusions and activated point mutants / intrinsic apoptotic signaling pathway in response to DNA damage / 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 / protein homodimerization activity / mitochondrion / nucleoplasm / membrane / nucleus / 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 (B-Cell lymphoma); contains BH1, BH2 regions ...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 (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 / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-E4Q / Induced myeloid leukemia cell differentiation protein Mcl-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.6 Å
AuthorsKasmirski, S. / Hargreaves, D.
CitationJournal: Nat Commun / Year: 2018
Title: Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia.
Authors: Tron, A.E. / Belmonte, M.A. / Adam, A. / Aquila, B.M. / Boise, L.H. / Chiarparin, E. / Cidado, J. / Embrey, K.J. / Gangl, E. / Gibbons, F.D. / Gregory, G.P. / Hargreaves, D. / Hendricks, J.A. ...Authors: Tron, A.E. / Belmonte, M.A. / Adam, A. / Aquila, B.M. / Boise, L.H. / Chiarparin, E. / Cidado, J. / Embrey, K.J. / Gangl, E. / Gibbons, F.D. / Gregory, G.P. / Hargreaves, D. / Hendricks, J.A. / Johannes, J.W. / Johnstone, R.W. / Kazmirski, S.L. / Kettle, J.G. / Lamb, M.L. / Matulis, S.M. / Nooka, A.K. / Packer, M.J. / Peng, B. / Rawlins, P.B. / Robbins, D.W. / Schuller, A.G. / Su, N. / Yang, W. / Ye, Q. / Zheng, X. / Secrist, J.P. / Clark, E.A. / Wilson, D.M. / Fawell, S.E. / Hird, A.W.
History
DepositionFeb 18, 2018Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 26, 2018Provider: repository / Type: Initial release
Revision 1.1May 8, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
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
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,4846
Polymers34,1732
Non-polymers1,3124
Water6,900383
1
A: Induced myeloid leukemia cell differentiation protein Mcl-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)17,6802
Polymers17,0861
Non-polymers5941
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Induced myeloid leukemia cell differentiation protein Mcl-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)17,8044
Polymers17,0861
Non-polymers7183
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)42.680, 64.519, 59.975
Angle α, β, γ (deg.)90.00, 98.82, 90.00
Int Tables number4
Space group name H-MP1211

-
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: 17086.443 Da / Num. of mol.: 2
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-E4Q / 7-[3-[(1,5-dimethylpyrazol-3-yl)methylsulfanylmethyl]-1,5-dimethyl-pyrazol-4-yl]-3-(3-naphthalen-1-yloxypropyl)-1~{H}-indole-2-carboxylic acid


Mass: 593.738 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C34H35N5O3S
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 383 / 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: 2.39 Å3/Da / Density % sol: 48.49 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / Details: 22% PEG MME 5K, 2% PEG 400, 0.1M MES pH 5.6

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E+ SUPERBRIGHT / Wavelength: 1.54 Å
DetectorType: RIGAKU SATURN 944+ / Detector: CCD / Date: Jan 14, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 1.6→64.52 Å / Num. obs: 34104 / % possible obs: 79.8 % / Redundancy: 3.2 % / Biso Wilson estimate: 17.11 Å2 / Net I/σ(I): 26
Reflection shellResolution: 1.6→1.68 Å / Redundancy: 1.6 % / Mean I/σ(I) obs: 6.3 / % possible all: 18.1

-
Processing

Software
NameVersionClassification
XDSdata reduction
SCALAdata scaling
BUSTER2.11.5 PACIOREKrefinement
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.6→29.5 Å / Cor.coef. Fo:Fc: 0.9269 / Cor.coef. Fo:Fc free: 0.9115 / SU R Cruickshank DPI: 0.122 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.13 / SU Rfree Blow DPI: 0.117 / SU Rfree Cruickshank DPI: 0.114
RfactorNum. reflection% reflectionSelection details
Rfree0.2263 1726 5.06 %RANDOM
Rwork0.1981 ---
obs0.1995 34077 80.15 %-
Displacement parametersBiso mean: 17.97 Å2
Baniso -1Baniso -2Baniso -3
1-0.026 Å20 Å21.6278 Å2
2---2.0555 Å20 Å2
3---2.0294 Å2
Refine analyzeLuzzati coordinate error obs: 0.203 Å
Refinement stepCycle: LAST / Resolution: 1.6→29.5 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2423 0 94 383 2900
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0082570HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.863471HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d939SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes62HARMONIC2
X-RAY DIFFRACTIONt_gen_planes468HARMONIC5
X-RAY DIFFRACTIONt_it2570HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.52
X-RAY DIFFRACTIONt_other_torsion16.2
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion317SEMIHARMONIC5
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_contact3462SEMIHARMONIC4
LS refinement shellResolution: 1.6→1.65 Å / Total num. of bins used: 17
RfactorNum. reflection% reflection
Rfree0.2946 21 4.7 %
Rwork0.244 426 -
all0.2465 447 -
obs--80.15 %
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)
10.7617-0.0043-0.22150.8486-0.30651.1533-0.003-0.0129-0.0568-0.00140.0236-0.03410.133-0.0456-0.0206-0.048-0.0053-0.0179-0.0945-0.0012-0.09529.7469-6.520918.2445
21.0653-0.1408-0.07711.0516-0.13841.05220.0102-0.03040.04890.0105-0.0024-0.0468-0.0834-0.0286-0.0078-0.09080.0067-0.0042-0.1022-0.0033-0.11256.254321.10211.7369
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ A|* }
2X-RAY DIFFRACTION2{ 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://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