[English] 日本語
Yorodumi
- PDB-5mvs: Crystal structure of Dot1L in complex with adenosine and inhibito... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5mvs
TitleCrystal structure of Dot1L in complex with adenosine and inhibitor CPD1 [N6-(2,6-dichlorophenyl)-N6-(pent-2-yn-1-yl)quinoline-4,6-diamine]
ComponentsHistone-lysine N-methyltransferase, H3 lysine-79 specific
KeywordsTRANSFERASE / inhibitor / complex / methyltransferase
Function / homology
Function and homology information


histone H3K79 trimethyltransferase activity / [histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / regulation of transcription regulatory region DNA binding / histone H3 methyltransferase activity / regulation of receptor signaling pathway via JAK-STAT / histone methyltransferase activity / heterochromatin formation / telomere organization / DNA damage checkpoint signaling ...histone H3K79 trimethyltransferase activity / [histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / regulation of transcription regulatory region DNA binding / histone H3 methyltransferase activity / regulation of receptor signaling pathway via JAK-STAT / histone methyltransferase activity / heterochromatin formation / telomere organization / DNA damage checkpoint signaling / PKMTs methylate histone lysines / gene expression / methylation / RNA polymerase II-specific DNA-binding transcription factor binding / nucleic acid binding / transcription coactivator activity / intracellular membrane-bounded organelle / DNA repair / positive regulation of cell population proliferation / positive regulation of transcription by RNA polymerase II / protein-containing complex / DNA binding / nucleoplasm / nucleus / cytoplasm
Similarity search - Function
434 Repressor (Amino-terminal Domain) - #60 / Histone H3-K79 methyltransferase, metazoa / Histone-lysine N-methyltransferase DOT1 domain / Histone H3-K79 methyltransferase / Histone methylation protein DOT1 / Histone-lysine N-methyltransferase DOT1 (EC 2.1.1.43) domain profile. / 434 Repressor (Amino-terminal Domain) / Vaccinia Virus protein VP39 / S-adenosyl-L-methionine-dependent methyltransferase superfamily / Rossmann fold ...434 Repressor (Amino-terminal Domain) - #60 / Histone H3-K79 methyltransferase, metazoa / Histone-lysine N-methyltransferase DOT1 domain / Histone H3-K79 methyltransferase / Histone methylation protein DOT1 / Histone-lysine N-methyltransferase DOT1 (EC 2.1.1.43) domain profile. / 434 Repressor (Amino-terminal Domain) / Vaccinia Virus protein VP39 / S-adenosyl-L-methionine-dependent methyltransferase superfamily / Rossmann fold / Orthogonal Bundle / 3-Layer(aba) Sandwich / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-5JJ / ADENOSINE / L(+)-TARTARIC ACID / Histone-lysine N-methyltransferase, H3 lysine-79 specific
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.18 Å
AuthorsBe, C. / Koch, E. / Gaul, C. / Stauffer, F. / Moebitz, H. / Scheufler, C.
CitationJournal: ACS Med Chem Lett / Year: 2017
Title: Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach.
Authors: Mobitz, H. / Machauer, R. / Holzer, P. / Vaupel, A. / Stauffer, F. / Ragot, C. / Caravatti, G. / Scheufler, C. / Fernandez, C. / Hommel, U. / Tiedt, R. / Beyer, K.S. / Chen, C. / Zhu, H. / Gaul, C.
History
DepositionJan 17, 2017Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 22, 2017Provider: repository / Type: Initial release
Revision 1.1Apr 5, 2017Group: Database references
Revision 1.2Jan 17, 2024Group: 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: Histone-lysine N-methyltransferase, H3 lysine-79 specific
B: Histone-lysine N-methyltransferase, H3 lysine-79 specific
hetero molecules


Theoretical massNumber of molelcules
Total (without water)78,3387
Polymers76,9132
Non-polymers1,4255
Water7,909439
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4200 Å2
ΔGint-10 kcal/mol
Surface area29860 Å2
MethodPISA
Unit cell
Length a, b, c (Å)158.211, 158.211, 73.826
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number173
Space group name H-MP63

-
Components

#1: Protein Histone-lysine N-methyltransferase, H3 lysine-79 specific / DOT1-like protein / Histone H3-K79 methyltransferase / H3-K79-HMTase / Lysine N-methyltransferase 4


Mass: 38456.594 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DOT1L, KIAA1814, KMT4 / Production host: Escherichia coli (E. coli)
References: UniProt: Q8TEK3, histone-lysine N-methyltransferase
#2: Chemical ChemComp-ADN / ADENOSINE


Mass: 267.241 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H13N5O4
#3: Chemical ChemComp-5JJ / N~6~-(2,6-dichlorophenyl)-N~6~-(pent-2-yn-1-yl)quinoline-4,6-diamine


Mass: 370.275 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C20H17Cl2N3
#4: Chemical ChemComp-TLA / L(+)-TARTARIC ACID


Mass: 150.087 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H6O6
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 439 / 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: 3.47 Å3/Da / Density % sol: 64.53 %
Crystal growTemperature: 293 K / Method: vapor diffusion / Details: 1.4M K/Na tartrate, 0.1M Hepes pH6.8

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.99999 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 8, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99999 Å / Relative weight: 1
ReflectionResolution: 2.18→25 Å / Num. obs: 55009 / % possible obs: 99.8 % / Redundancy: 10.1 % / Biso Wilson estimate: 40.25 Å2 / Rsym value: 0.104 / Net I/σ(I): 18.02
Reflection shellResolution: 2.18→2.24 Å / Redundancy: 8.6 % / Mean I/σ(I) obs: 2.51 / % possible all: 97.7

-
Processing

Software
NameVersionClassification
BUSTER2.11.5refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1nw3

1nw3


Resolution: 2.18→21.98 Å / Cor.coef. Fo:Fc: 0.9496 / Cor.coef. Fo:Fc free: 0.9467 / SU R Cruickshank DPI: 0.154 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.156 / SU Rfree Blow DPI: 0.131 / SU Rfree Cruickshank DPI: 0.131
RfactorNum. reflection% reflectionSelection details
Rfree0.1874 2748 5 %RANDOM
Rwork0.1687 ---
obs0.1696 54952 99.82 %-
Displacement parametersBiso mean: 49.02 Å2
Baniso -1Baniso -2Baniso -3
1-5.8661 Å20 Å20 Å2
2--5.8661 Å20 Å2
3----11.7322 Å2
Refine analyzeLuzzati coordinate error obs: 0.268 Å
Refinement stepCycle: 1 / Resolution: 2.18→21.98 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5140 0 98 439 5677
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.015379HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.977317HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1803SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes133HARMONIC2
X-RAY DIFFRACTIONt_gen_planes769HARMONIC5
X-RAY DIFFRACTIONt_it5379HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.03
X-RAY DIFFRACTIONt_other_torsion15.87
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion688SEMIHARMONIC5
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_contact6315SEMIHARMONIC4
LS refinement shellResolution: 2.18→2.24 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.2535 198 5 %
Rwork0.2069 3760 -
all0.2093 3958 -
obs--99.82 %
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)
12.1219-0.96210.38662.0418-0.20820.73470.0053-0.1771-0.04590.19020.0278-0.444-0.08110.1178-0.0331-0.1485-0.0143-0.0355-0.10060.0106-0.067943.9622-8.10688.6723
22.2005-0.5673-0.48931.5670.10230.49450.0256-0.0972-0.370.0478-0.0841-0.25910.17020.02990.0585-0.11340.0354-0.0288-0.13810.0435-0.021435.7862-37.26698.5173
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ A|* L|* }
2X-RAY DIFFRACTION2{ B|* M|* }

+
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://pdbjlvh1.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