[English] 日本語
Yorodumi
- PDB-4mkc: Crystal Structure of Anaplastic Lymphoma Kinase Complexed with LDK378 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4mkc
TitleCrystal Structure of Anaplastic Lymphoma Kinase Complexed with LDK378
ComponentsALK tyrosine kinase receptor
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / kinase domain / phosphotransferase / ATP binding / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


ASP-3026-resistant ALK mutants / NVP-TAE684-resistant ALK mutants / alectinib-resistant ALK mutants / brigatinib-resistant ALK mutants / ceritinib-resistant ALK mutants / crizotinib-resistant ALK mutants / lorlatinib-resistant ALK mutants / MDK and PTN in ALK signaling / receptor signaling protein tyrosine kinase activator activity / regulation of dopamine receptor signaling pathway ...ASP-3026-resistant ALK mutants / NVP-TAE684-resistant ALK mutants / alectinib-resistant ALK mutants / brigatinib-resistant ALK mutants / ceritinib-resistant ALK mutants / crizotinib-resistant ALK mutants / lorlatinib-resistant ALK mutants / MDK and PTN in ALK signaling / receptor signaling protein tyrosine kinase activator activity / regulation of dopamine receptor signaling pathway / response to environmental enrichment / ALK mutants bind TKIs / swimming behavior / positive regulation of dendrite development / regulation of neuron differentiation / adult behavior / Signaling by ALK / neuron development / negative regulation of lipid catabolic process / energy homeostasis / peptidyl-tyrosine autophosphorylation / cell surface receptor protein tyrosine kinase signaling pathway / transmembrane receptor protein tyrosine kinase activity / hippocampus development / receptor protein-tyrosine kinase / Signaling by ALK fusions and activated point mutants / positive regulation of NF-kappaB transcription factor activity / heparin binding / regulation of cell population proliferation / regulation of apoptotic process / protein tyrosine kinase activity / protein autophosphorylation / receptor complex / phosphorylation / signal transduction / protein-containing complex / extracellular exosome / ATP binding / identical protein binding / plasma membrane
Similarity search - Function
Glycine rich protein / MAM domain, meprin/A5/mu / MAM domain / MAM domain profile. / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A repeat / LDL receptor-like superfamily / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Tyrosine-protein kinase, catalytic domain ...Glycine rich protein / MAM domain, meprin/A5/mu / MAM domain / MAM domain profile. / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A repeat / LDL receptor-like superfamily / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Concanavalin A-like lectin/glucanase domain superfamily / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-4MK / ALK tyrosine kinase receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.01 Å
AuthorsLee, C.C. / Spraggon, G.
CitationJournal: Cancer Discov / Year: 2014
Title: The ALK Inhibitor Ceritinib Overcomes Crizotinib Resistance in Non-Small Cell Lung Cancer.
Authors: Friboulet, L. / Li, N. / Katayama, R. / Lee, C.C. / Gainor, J.F. / Crystal, A.S. / Michellys, P.Y. / Awad, M.M. / Yanagitani, N. / Kim, S. / Pferdekamper, A.C. / Li, J. / Kasibhatla, S. / ...Authors: Friboulet, L. / Li, N. / Katayama, R. / Lee, C.C. / Gainor, J.F. / Crystal, A.S. / Michellys, P.Y. / Awad, M.M. / Yanagitani, N. / Kim, S. / Pferdekamper, A.C. / Li, J. / Kasibhatla, S. / Sun, F. / Sun, X. / Hua, S. / McNamara, P. / Mahmood, S. / Lockerman, E.L. / Fujita, N. / Nishio, M. / Harris, J.L. / Shaw, A.T. / Engelman, J.A.
History
DepositionSep 4, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 9, 2014Provider: repository / Type: Initial release
Revision 1.1Jun 18, 2014Group: Database references
Revision 1.2Apr 29, 2015Group: Non-polymer description
Revision 1.3Sep 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif / struct_site
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI ..._chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: ALK tyrosine kinase receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,3584
Polymers41,6161
Non-polymers7423
Water3,153175
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)51.640, 57.650, 105.990
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121
Details1/2-x, -y, 1/2+z

-
Components

#1: Protein ALK tyrosine kinase receptor / Anaplastic lymphoma kinase


Mass: 41615.500 Da / Num. of mol.: 1 / Fragment: CATALYTIC DOMAIN residues 1072-1410 / Mutation: S1281G
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ALK / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q9UM73, receptor protein-tyrosine kinase
#2: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#3: Chemical ChemComp-4MK / 5-chloro-N~2~-[5-methyl-4-(piperidin-4-yl)-2-(propan-2-yloxy)phenyl]-N~4~-[2-(propan-2-ylsulfonyl)phenyl]pyrimidine-2,4-diamine / Ceritinib / LDK378


Mass: 558.135 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C28H36ClN5O3S
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 175 / 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: 1.9 Å3/Da / Density % sol: 35.11 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, hanging drop
Details: 20% PEG3350, 0.2M Sodium acetate trihydrate, VAPOR DIFFUSION, HANGING DROP, temperature 277.15K

-
Data collection

DiffractionMean temperature: 200 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.9765 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: May 16, 2013
RadiationMonochromator: Single crystal, cylindrically bent, Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9765 Å / Relative weight: 1
ReflectionResolution: 2.01→46.42 Å / Num. obs: 21666 / % possible obs: 99.5 % / Biso Wilson estimate: 32.51 Å2 / Rsym value: 0.09
Reflection shellResolution: 2.01→2.04 Å / % possible all: 90.3

-
Processing

Software
NameVersionClassification
HKL-2000data collection
BUSTER2.11.2refinement
DENZOdata reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3L9P

3l9p


Resolution: 2.01→46.42 Å / Cor.coef. Fo:Fc: 0.9525 / Cor.coef. Fo:Fc free: 0.9299 / SU R Cruickshank DPI: 0.167 / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.2179 1108 5.11 %RANDOM
Rwork0.1711 ---
obs0.1734 21717 99.74 %-
Displacement parametersBiso mean: 37.37 Å2
Baniso -1Baniso -2Baniso -3
1-5.0303 Å20 Å20 Å2
2--2.4807 Å20 Å2
3----7.511 Å2
Refine analyzeLuzzati coordinate error obs: 0.229 Å
Refinement stepCycle: LAST / Resolution: 2.01→46.42 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2385 0 50 175 2610
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.012523HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.023431HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d871SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes58HARMONIC2
X-RAY DIFFRACTIONt_gen_planes369HARMONIC5
X-RAY DIFFRACTIONt_it2523HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.95
X-RAY DIFFRACTIONt_other_torsion16.78
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion318SEMIHARMONIC5
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_contact3107SEMIHARMONIC4
LS refinement shellResolution: 2.01→2.11 Å / Total num. of bins used: 11
RfactorNum. reflection% reflection
Rfree0.2522 131 4.74 %
Rwork0.2061 2634 -
all0.2083 2765 -
obs--99.74 %
Refinement TLS params.Method: refined / Origin x: -13.4437 Å / Origin y: 10.288 Å / Origin z: -16.7468 Å
111213212223313233
T-0.1017 Å2-0.0112 Å20.0204 Å2--0.075 Å20.0122 Å2---0.0783 Å2
L0.9979 °2-0.4054 °2-0.1876 °2-1.0879 °20.3649 °2--1.3598 °2
S0.0214 Å °-0.1022 Å °-0.0074 Å °0.0473 Å °0.0692 Å °0.0271 Å °-0.049 Å °0.0837 Å °-0.0907 Å °
Refinement TLS groupSelection details: { A|1093 - A|1401 }

+
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