[English] 日本語
Yorodumi
- PDB-8gmc: CRYSTAL STRUCTURE OF AP2 ASSOCIATED KINASE 1 COMPLEXED WITH 5-[(4... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8gmc
TitleCRYSTAL STRUCTURE OF AP2 ASSOCIATED KINASE 1 COMPLEXED WITH 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
ComponentsAP2-associated protein kinase 1
KeywordsTRANSFERASE / AP2 ASSOCIATED KINASE 1 / AAK1 / kinase / ligand inhibitor
Function / homology
Function and homology information


presynaptic endocytosis / regulation of clathrin-dependent endocytosis / AP-2 adaptor complex binding / membrane organization / Notch binding / clathrin-coated vesicle / positive regulation of Notch signaling pathway / cell leading edge / clathrin-coated pit / terminal bouton ...presynaptic endocytosis / regulation of clathrin-dependent endocytosis / AP-2 adaptor complex binding / membrane organization / Notch binding / clathrin-coated vesicle / positive regulation of Notch signaling pathway / cell leading edge / clathrin-coated pit / terminal bouton / regulation of protein localization / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / protein stabilization / non-specific serine/threonine protein kinase / protein phosphorylation / protein serine kinase activity / intracellular membrane-bounded organelle / 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-YFV / AP2-associated protein kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å
AuthorsMuckelbauer, J.K.
Funding support1items
OrganizationGrant numberCountry
Other private
CitationJournal: Med.Chem.Res. / Year: 2023
Title: Discovery of pyrrolo[2,1- f ][1,2,4]triazine-based inhibitors of adaptor protein 2-associated kinase 1 for the treatment of pain.
Authors: Dzierba, C.D. / Dasgupta, B. / Karageorge, G. / Kostich, W. / Hamman, B. / Allen, J. / Esposito, K.M. / Padmanabha, R. / Grace, J. / Lentz, K. / Morrison, J. / Morgan, D. / Easton, A. / ...Authors: Dzierba, C.D. / Dasgupta, B. / Karageorge, G. / Kostich, W. / Hamman, B. / Allen, J. / Esposito, K.M. / Padmanabha, R. / Grace, J. / Lentz, K. / Morrison, J. / Morgan, D. / Easton, A. / Bourin, C. / Browning, M.R. / Rajamani, R. / Good, A. / Parker, D.D. / Muckelbauer, J.K. / Khan, J. / Camac, D. / Ghosh, K. / Halan, V. / Lippy, J.S. / Santone, K.S. / Denton, R.R. / Westphal, R. / Bristow, L.J. / Conway, C.M. / Bronson, J.J. / Macor, J.E.
History
DepositionMar 24, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 12, 2023Provider: repository / Type: Initial release
Revision 1.1Oct 25, 2023Group: Data collection / Category: chem_comp_atom / chem_comp_bond

-
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)73,4728
Polymers72,1912
Non-polymers1,2816
Water1,33374
1
A: AP2-associated protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,8325
Polymers36,0951
Non-polymers7374
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: AP2-associated protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,6403
Polymers36,0951
Non-polymers5452
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)74.778, 74.778, 310.850
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number92
Space group name H-MP41212

-
Components

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


Mass: 36095.391 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: AAK1, KIAA1048 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: Q2M2I8, 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.: 2 / Source method: obtained synthetically / Formula: C23H28N8S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 74 / 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: 3.01 Å3/Da / Density % sol: 59.13 %
Crystal growTemperature: 296 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 1.2M AmSO4, 0.1M tri-Na Citrate pH 6.0, 3% isopropanol, 296K

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-BM / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Jul 24, 2008
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.5→50 Å / Num. obs: 31551 / % possible obs: 99.5 % / Redundancy: 4.2 % / Rmerge(I) obs: 0.09 / Net I/σ(I): 18.4
Reflection shellResolution: 2.5→2.59 Å / Redundancy: 4.2 % / Rmerge(I) obs: 0.633 / Mean I/σ(I) obs: 2.5 / Num. unique obs: 5895 / % possible all: 100

-
Processing

Software
NameClassification
BUSTERrefinement
HKL-2000data reduction
PHASERphasing
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 7rj6

7rj6


Resolution: 2.5→32.53 Å / Cor.coef. Fo:Fc: 0.913 / Cor.coef. Fo:Fc free: 0.896 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.237
RfactorNum. reflection% reflectionSelection details
Rfree0.256 1592 5.05 %RANDOM
Rwork0.227 ---
obs0.228 31551 99.5 %-
Displacement parametersBiso mean: 44.67 Å2
Baniso -1Baniso -2Baniso -3
1--4.2512 Å20 Å20 Å2
2---4.2512 Å20 Å2
3---8.5025 Å2
Refine analyzeLuzzati coordinate error obs: 0.381 Å
Refinement stepCycle: LAST / Resolution: 2.5→32.53 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4442 0 84 74 4600
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.014618HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.146281HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1523SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes107HARMONIC2
X-RAY DIFFRACTIONt_gen_planes724HARMONIC5
X-RAY DIFFRACTIONt_it4618HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.14
X-RAY DIFFRACTIONt_other_torsion18.12
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion615SEMIHARMONIC5
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_contact5275SEMIHARMONIC4
LS refinement shellResolution: 2.5→2.58 Å / Total num. of bins used: 16
RfactorNum. reflection% reflection
Rfree0.3142 140 4.91 %
Rwork0.2672 2714 -
all0.2696 2854 -
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