[English] 日本語
Yorodumi
- PDB-7rj6: CRYSTAL STRUCTURE OF AP2 ASSOCIATED KINASE 1 ISOFORM 1 COMPLEXED ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7rj6
TitleCRYSTAL STRUCTURE OF AP2 ASSOCIATED KINASE 1 ISOFORM 1 COMPLEXED WITH LIGAND (2R)-2-AMINO-N-[3-(DIFLUOROM ETHOXY)-4-(1,3-OXAZOL-5-YL)PHENYL]-4-METHYLPENTANAMIDE
ComponentsAP2-associated protein kinase 1
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / KINASE / AAK1 / LIGAND / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


regulation of clathrin-dependent endocytosis / clathrin complex / presynaptic endocytosis / AP-2 adaptor complex binding / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / Notch binding / clathrin-coated vesicle / positive regulation of Notch signaling pathway / cell leading edge ...regulation of clathrin-dependent endocytosis / clathrin complex / presynaptic endocytosis / AP-2 adaptor complex binding / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / Notch binding / clathrin-coated vesicle / positive regulation of Notch signaling pathway / cell leading edge / calyx of Held / clathrin-coated pit / terminal bouton / regulation of protein localization / presynapse / protein stabilization / non-specific serine/threonine protein kinase / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / ATP binding / plasma membrane / cytosol
Similarity search - Function
: / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Chem-5OI / Chem-YFV / AP2-associated protein kinase 1
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.132 Å
AuthorsMuckelbauer, J.
CitationJournal: J.Med.Chem. / Year: 2022
Title: Bicyclic Heterocyclic Replacement of an Aryl Amide Leading to Potent and Kinase-Selective Adaptor Protein 2-Associated Kinase 1 Inhibitors.
Authors: Hartz, R.A. / Ahuja, V.T. / Nara, S.J. / Kumar, C.M.V. / Manepalli, R.K.V.L.P. / Sarvasiddhi, S.K. / Honkhambe, S. / Patankar, V. / Dasgupta, B. / Rajamani, R. / Muckelbauer, J.K. / Camac, D. ...Authors: Hartz, R.A. / Ahuja, V.T. / Nara, S.J. / Kumar, C.M.V. / Manepalli, R.K.V.L.P. / Sarvasiddhi, S.K. / Honkhambe, S. / Patankar, V. / Dasgupta, B. / Rajamani, R. / Muckelbauer, J.K. / Camac, D.M. / Ghosh, K. / Pokross, M. / Kiefer, S.E. / Brown, J.M. / Hunihan, L. / Gulianello, M. / Lewis, M. / Lippy, J.S. / Surti, N. / Hamman, B.D. / Allen, J. / Kostich, W.A. / Bronson, J.J. / Macor, J.E. / Dzierba, C.D.
History
DepositionJul 20, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 23, 2022Provider: repository / Type: Initial release
Revision 1.1Mar 23, 2022Group: 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 1.2Apr 3, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: AP2-associated protein kinase 1
B: AP2-associated protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)73,29210
Polymers71,9562
Non-polymers1,3358
Water4,252236
1
A: AP2-associated protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,5233
Polymers35,9781
Non-polymers5452
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: AP2-associated protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,7697
Polymers35,9781
Non-polymers7916
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)91.831, 91.831, 170.871
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number152
Space group name H-MP3121

-
Components

#1: Protein AP2-associated protein kinase 1 / Adaptor-associated kinase 1


Mass: 35978.223 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Aak1, Kiaa1048 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: Q3UHJ0, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-YFV / 5-[(4-aminopiperidin-1-yl)methyl]-N-{3-[5-(propan-2-yl)-1,3,4-thiadiazol-2-yl]phenyl}pyrrolo[2,1-f][1,2,4]triazin-4-amine


Mass: 448.587 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H28N8S
#3: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: SO4
#4: Chemical ChemComp-5OI / (1S)-1-[4-ethyl-6-(1,3-oxazol-5-yl)quinazolin-2-yl]-3-methylbutan-1-amine


Mass: 310.393 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H22N4O / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 236 / 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: 2.89 Å3/Da / Density % sol: 57.45 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop / pH: 5.5
Details: 0.9 M ammonium sulfate, 0.14 M sodium chloride, 0.1 M Bis-Tris pH 5.5, and 1% PEG 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 1, 2010 / Details: Kirkpatrick-Baez Mirrors
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.13→170.87 Å / Num. obs: 47322 / % possible obs: 100 % / Redundancy: 9.9 % / Biso Wilson estimate: 36.73 Å2 / Rmerge(I) obs: 0.078 / Net I/av σ(I): 7.5 / Net I/σ(I): 20.2
Reflection shellResolution: 2.13→2.25 Å / Redundancy: 10.3 % / Mean I/σ(I) obs: 4.8 / Num. unique obs: 6801 / Rsym value: 0.49 / % possible all: 100

-
Processing

Software
NameVersionClassification
SCALA3.3.15data scaling
BUSTER2.11.7refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: In house model

Resolution: 2.132→72.1 Å / Cor.coef. Fo:Fc: 0.935 / Cor.coef. Fo:Fc free: 0.925 / SU R Cruickshank DPI: 0.319 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.187 / SU Rfree Blow DPI: 0.149 / SU Rfree Cruickshank DPI: 0.148
Details: HYDROGENS WERE FULLY REFINED WITH ZERO OCCUPANCY AT NUCLEAR POSITION. REFINEMENT NOTES. NUMBER OF REFINEMENT NOTES : 1 NOTE 1 : IDEAL-DIST CONTACT TERM CONTACT SETUP. ALL ATOMS HAVE CCP4 ATOM TYPE FROM LIBRARY
RfactorNum. reflection% reflectionSelection details
Rfree0.2151 2387 5.05 %RANDOM
Rwork0.2015 ---
obs0.2022 47267 100 %-
Displacement parametersBiso max: 113.6 Å2 / Biso mean: 39.21 Å2 / Biso min: 17.08 Å2
Baniso -1Baniso -2Baniso -3
1-0.6556 Å20 Å20 Å2
2--0.6556 Å20 Å2
3----1.3112 Å2
Refine analyzeLuzzati coordinate error obs: 0.29 Å
Refinement stepCycle: final / Resolution: 2.132→72.1 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4665 0 85 236 4986
Biso mean--47.72 39.12 -
Num. residues----604
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d2807SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes1586HARMONIC5
X-RAY DIFFRACTIONt_it4852HARMONIC10
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion631SEMIHARMONIC5
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_contact7103SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d9431HARMONIC20.008
X-RAY DIFFRACTIONt_angle_deg17013HARMONIC20.98
X-RAY DIFFRACTIONt_omega_torsion3.41
X-RAY DIFFRACTIONt_other_torsion15.08
LS refinement shellResolution: 2.132→2.15 Å / Rfactor Rfree error: 0
RfactorNum. reflection% reflection
Rfree0.2651 49 5.18 %
Rwork0.2165 897 -
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