[English] 日本語
Yorodumi
- PDB-6udu: X-ray co-crystal structure of compound 8 bound to human Mcl-1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6udu
TitleX-ray co-crystal structure of compound 8 bound to human Mcl-1
ComponentsInduced myeloid leukemia cell differentiation protein Mcl-1
KeywordsAPOPTOSIS/INHIBITOR / protein-protein interaction / apoptosis / inhibitor / 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 / Bcl-2 family protein complex / mitochondrial fusion / BH domain binding / 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 / Bcl-2 family protein complex / mitochondrial fusion / BH domain binding / 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 / release of cytochrome c from mitochondria / negative regulation of autophagy / response to cytokine / intrinsic apoptotic signaling pathway in response to DNA damage / Signaling by ALK fusions and activated point mutants / channel activity / Interleukin-4 and Interleukin-13 signaling / regulation of apoptotic process / mitochondrial outer membrane / positive regulation of apoptotic process / protein heterodimerization activity / DNA damage response / negative regulation of apoptotic process / 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-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 / BCL2-like apoptosis inhibitors family profile. / Apoptosis regulator proteins, Bcl-2 family / Bcl-2-like superfamily / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-Q4Y / Induced myeloid leukemia cell differentiation protein Mcl-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.75 Å
AuthorsHuang, X. / Whittington, D.
CitationJournal: J.Med.Chem. / Year: 2019
Title: Discovery and in Vivo Evaluation of Macrocyclic Mcl-1 Inhibitors Featuring an alpha-Hydroxy Phenylacetic Acid Pharmacophore or Bioisostere.
Authors: Rescourio, G. / Gonzalez, A.Z. / Jabri, S. / Belmontes, B. / Moody, G. / Whittington, D. / Huang, X. / Caenepeel, S. / Cardozo, M. / Cheng, A.C. / Chow, D. / Dou, H. / Jones, A. / Kelly, R.C. ...Authors: Rescourio, G. / Gonzalez, A.Z. / Jabri, S. / Belmontes, B. / Moody, G. / Whittington, D. / Huang, X. / Caenepeel, S. / Cardozo, M. / Cheng, A.C. / Chow, D. / Dou, H. / Jones, A. / Kelly, R.C. / Li, Y. / Lizarzaburu, M. / Lo, M.C. / Mallari, R. / Meleza, C. / Rew, Y. / Simonovich, S. / Sun, D. / Turcotte, S. / Yan, X. / Wong, S.G. / Yanez, E. / Zancanella, M. / Houze, J. / Medina, J.C. / Hughes, P.E. / Brown, S.P.
History
DepositionSep 19, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 4, 2019Provider: repository / Type: Initial release
Revision 1.1Dec 11, 2019Group: 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 1.2Mar 13, 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
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,4612
Polymers17,9221
Non-polymers5391
Water1,820101
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area8880 Å2
2
A: Induced myeloid leukemia cell differentiation protein Mcl-1
hetero molecules

A: Induced myeloid leukemia cell differentiation protein Mcl-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,9234
Polymers35,8452
Non-polymers1,0782
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation3_557-x,y,-z+5/21
Buried area1990 Å2
ΔGint-11 kcal/mol
Surface area15780 Å2
MethodPISA
Unit cell
Length a, b, c (Å)43.510, 89.427, 84.874
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number20
Space group name H-MC2221
Components on special symmetry positions
IDModelComponents
11A-585-

HOH

-
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: 17922.344 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: Chemical ChemComp-Q4Y / (4S,11E,17R)-6'-chloro-17-hydroxy-14-methyl-15-oxo-3',4',8,9,10,13,14,15,16,17-decahydro-2'H,3H,5H,7H-spiro[1,18-(ethanediylidene)[1,4]oxazepino[4,3-a][1,8]diazacyclopentadecine-4,1'-naphthalene]-17-carboxylic acid


Mass: 539.062 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C30H35ClN2O5 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 101 / 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: 2.31 Å3/Da / Density % sol: 46.77 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / Details: 0.1 M Tris pH 8.0, 3% Ethanol, 36% PEG6000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 0.97741 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Sep 20, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97741 Å / Relative weight: 1
ReflectionResolution: 1.75→50 Å / Num. obs: 17186 / % possible obs: 100 % / Redundancy: 5.89 % / Rmerge(I) obs: 0.09 / Net I/σ(I): 7.8
Reflection shellResolution: 1.75→1.81 Å / Rmerge(I) obs: 0.961 / Num. unique obs: 1701

-
Processing

Software
NameVersionClassification
REFMAC5.6.0117refinement
PDB_EXTRACT3.25data extraction
DENZOdata reduction
SCALEPACKdata scaling
REFMACphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.75→44.71 Å / Cor.coef. Fo:Fc: 0.966 / Cor.coef. Fo:Fc free: 0.956 / SU B: 2.62 / SU ML: 0.083 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.122 / ESU R Free: 0.119
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2289 854 5 %RANDOM
Rwork0.1894 ---
obs0.1913 16252 99.98 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 83.11 Å2 / Biso mean: 30.234 Å2 / Biso min: 18.84 Å2
Baniso -1Baniso -2Baniso -3
1--0.68 Å20 Å20 Å2
2--1.28 Å20 Å2
3----0.59 Å2
Refinement stepCycle: final / Resolution: 1.75→44.71 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1255 0 38 101 1394
Biso mean--27.65 42.19 -
Num. residues----156
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.021317
X-RAY DIFFRACTIONr_bond_other_d0.0010.02930
X-RAY DIFFRACTIONr_angle_refined_deg1.0851.981776
X-RAY DIFFRACTIONr_angle_other_deg0.833.0042201
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.235155
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.78523.12564
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.37915240
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.7971514
X-RAY DIFFRACTIONr_chiral_restr0.0640.2192
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.021448
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02278
LS refinement shellResolution: 1.75→1.795 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.366 59 -
Rwork0.258 1078 -
all-1137 -
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