[English] 日本語
Yorodumi
- PDB-4u43: MAP4K4 in complex with inhibitor (compound 6) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4u43
TitleMAP4K4 in complex with inhibitor (compound 6)
ComponentsMitogen-activated protein kinase kinase kinase kinase 4
KeywordsTransferase/Transferase inhibitor / kinase / Transferase-Transferase inhibitor complex
Function / homology
Function and homology information


positive regulation of ARF protein signal transduction / MAP kinase kinase kinase kinase activity / creatine kinase activity / positive regulation of hippo signaling / positive regulation of keratinocyte migration / positive regulation of focal adhesion disassembly / negative regulation of cell-matrix adhesion / regulation of MAPK cascade / positive regulation of focal adhesion assembly / regulation of JNK cascade ...positive regulation of ARF protein signal transduction / MAP kinase kinase kinase kinase activity / creatine kinase activity / positive regulation of hippo signaling / positive regulation of keratinocyte migration / positive regulation of focal adhesion disassembly / negative regulation of cell-matrix adhesion / regulation of MAPK cascade / positive regulation of focal adhesion assembly / regulation of JNK cascade / neuron projection morphogenesis / positive regulation of GTPase activity / MAPK cascade / microtubule binding / Oxidative Stress Induced Senescence / non-specific serine/threonine protein kinase / intracellular signal transduction / positive regulation of cell migration / protein phosphorylation / protein serine kinase activity / focal adhesion / protein serine/threonine kinase activity / negative regulation of apoptotic process / ATP binding / cytoplasm
Similarity search - Function
: / Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2 / CNH domain / Citron homology (CNH) domain / Citron homology (CNH) domain profile. / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Serine/threonine-protein kinase, active site ...: / Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2 / CNH domain / Citron homology (CNH) domain / Citron homology (CNH) domain profile. / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / 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-3D8 / Mitogen-activated protein kinase kinase kinase kinase 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.18 Å
AuthorsHarris, S.F. / Wu, P. / Coons, M.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2014
Title: Fragment-based identification and optimization of a class of potent pyrrolo[2,1-f][1,2,4]triazine MAP4K4 inhibitors.
Authors: Wang, L. / Stanley, M. / Boggs, J.W. / Crawford, T.D. / Bravo, B.J. / Giannetti, A.M. / Harris, S.F. / Magnuson, S.R. / Nonomiya, J. / Schmidt, S. / Wu, P. / Ye, W. / Gould, S.E. / Murray, L. ...Authors: Wang, L. / Stanley, M. / Boggs, J.W. / Crawford, T.D. / Bravo, B.J. / Giannetti, A.M. / Harris, S.F. / Magnuson, S.R. / Nonomiya, J. / Schmidt, S. / Wu, P. / Ye, W. / Gould, S.E. / Murray, L.J. / Ndubaku, C.O. / Chen, H.
History
DepositionJul 23, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 3, 2014Provider: repository / Type: Initial release
Revision 1.1Oct 1, 2014Group: Database references
Revision 1.2Nov 22, 2017Group: Database references / Derived calculations ...Database references / Derived calculations / Other / Refinement description / Source and taxonomy
Category: citation / entity_src_gen ...citation / entity_src_gen / pdbx_database_status / pdbx_struct_oper_list / software
Item: _citation.journal_id_CSD / _entity_src_gen.pdbx_alt_source_flag ..._citation.journal_id_CSD / _entity_src_gen.pdbx_alt_source_flag / _pdbx_database_status.pdb_format_compatible / _pdbx_struct_oper_list.symmetry_operation / _software.classification
Revision 1.3Dec 27, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / refine_hist
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _refine_hist.number_atoms_total / _refine_hist.pdbx_number_atoms_nucleic_acid / _refine_hist.pdbx_number_atoms_protein

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Mitogen-activated protein kinase kinase kinase kinase 4
B: Mitogen-activated protein kinase kinase kinase kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)75,9513
Polymers75,7402
Non-polymers2111
Water3,747208
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3380 Å2
ΔGint-16 kcal/mol
Surface area26250 Å2
MethodPISA
2
A: Mitogen-activated protein kinase kinase kinase kinase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,0812
Polymers37,8701
Non-polymers2111
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
B: Mitogen-activated protein kinase kinase kinase kinase 4


Theoretical massNumber of molelcules
Total (without water)37,8701
Polymers37,8701
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)75.492, 80.643, 102.335
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Mitogen-activated protein kinase kinase kinase kinase 4 / HPK/GCK-like kinase HGK / MAPK/ERK kinase kinase kinase 4 / MEKKK 4 / Nck-interacting kinase


Mass: 37870.078 Da / Num. of mol.: 2 / Fragment: kinase domain (UNP residues 2-328)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAP4K4, HGK, KIAA0687, NIK / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): Sf9
References: UniProt: O95819, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-3D8 / N-(pyridin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine


Mass: 211.223 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C11H9N5
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 208 / 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: 2.06 Å3/Da / Density % sol: 40.19 %
Crystal growTemperature: 292 K / Method: vapor diffusion, sitting drop / pH: 8.3 / Details: 0.2 M potassium citrate, pH 8.3, 20% PEG 3350

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 1.1001 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Oct 17, 2010
RadiationMonochromator: KOHZU Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.1001 Å / Relative weight: 1
ReflectionResolution: 2.18→50 Å / Num. obs: 33286 / % possible obs: 99.9 % / Redundancy: 6.1 % / Biso Wilson estimate: 47.76 Å2 / Rmerge(I) obs: 0.064 / Χ2: 1.034 / Net I/av σ(I): 26.119 / Net I/σ(I): 9.3 / Num. measured all: 203453
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2% possible all
2.18-2.266.20.56532621.025100
2.26-2.356.20.39632851.011100
2.35-2.466.20.28932761.046100
2.46-2.586.20.23232861.048100
2.58-2.756.20.16332851.029100
2.75-2.966.20.11333241.046100
2.96-3.266.20.07733351.018100
3.26-3.736.10.07333151.015100
3.73-4.760.04933911.052100
4.7-505.80.03535271.04899.5

-
Processing

Software
NameVersionClassificationNB
SCALEPACKdata scaling
PDB_EXTRACT3.14data extraction
BUSTER2.9.1refinement
RefinementResolution: 2.18→29.08 Å / SU R Cruickshank DPI: 0.263 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.27 / SU Rfree Blow DPI: 0.204 / SU Rfree Cruickshank DPI: 0.205
RfactorNum. reflection% reflectionSelection details
Rfree0.2425 1703 5.13 %RANDOM
Rwork0.1964 ---
obs0.1987 33223 99.9 %-
Displacement parametersBiso max: 156.08 Å2 / Biso mean: 58.13 Å2 / Biso min: 27.13 Å2
Baniso -1Baniso -2Baniso -3
1--10.733 Å20 Å20 Å2
2--12.0563 Å20 Å2
3----1.3233 Å2
Refine analyzeLuzzati coordinate error obs: 0.289 Å
Refinement stepCycle: final / Resolution: 2.18→29.08 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4754 0 16 208 4978
Biso mean--46.35 53.03 -
Num. residues----589
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1739SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes125HARMONIC2
X-RAY DIFFRACTIONt_gen_planes708HARMONIC5
X-RAY DIFFRACTIONt_it4909HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion628SEMIHARMONIC5
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_contact5815SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d4909HARMONIC20.009
X-RAY DIFFRACTIONt_angle_deg6641HARMONIC21.1
X-RAY DIFFRACTIONt_omega_torsion2.99
X-RAY DIFFRACTIONt_other_torsion20.3
LS refinement shellResolution: 2.18→2.25 Å / Total num. of bins used: 17
RfactorNum. reflection% reflection
Rfree0.2876 133 4.71 %
Rwork0.2378 2693 -
all0.24 2826 -
obs--99.9 %

+
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