[English] 日本語
Yorodumi
- PDB-4obq: MAP4K4 in complex with inhibitor (compound 31), N-[3-(4-AMINOQUIN... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4obq
TitleMAP4K4 in complex with inhibitor (compound 31), N-[3-(4-AMINOQUINAZOLIN-6-YL)-5-FLUOROPHENYL]-2-(PYRROLIDIN-1-YL)ACETAMIDE
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-2QT / Mitogen-activated protein kinase kinase kinase kinase 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.19 Å
AuthorsHarris, S.F. / Wu, P. / Coons, M.
CitationJournal: J.Med.Chem. / Year: 2014
Title: Discovery of Selective 4-Amino-pyridopyrimidine Inhibitors of MAP4K4 Using Fragment-Based Lead Identification and Optimization.
Authors: Crawford, T.D. / Ndubaku, C.O. / Chen, H. / Boggs, J.W. / Bravo, B.J. / Delatorre, K. / Giannetti, A.M. / Gould, S.E. / Harris, S.F. / Magnuson, S.R. / McNamara, E. / Murray, L.J. / ...Authors: Crawford, T.D. / Ndubaku, C.O. / Chen, H. / Boggs, J.W. / Bravo, B.J. / Delatorre, K. / Giannetti, A.M. / Gould, S.E. / Harris, S.F. / Magnuson, S.R. / McNamara, E. / Murray, L.J. / Nonomiya, J. / Sambrone, A. / Schmidt, S. / Smyczek, T. / Stanley, M. / Vitorino, P. / Wang, L. / West, K. / Wu, P. / Ye, W.
History
DepositionJan 7, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 23, 2014Provider: repository / Type: Initial release
Revision 1.1May 7, 2014Group: Database references
Revision 1.2Feb 28, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_struct_conn_angle / struct_conn / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _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: 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)76,3255
Polymers75,7402
Non-polymers5853
Water3,999222
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2860 Å2
ΔGint-23 kcal/mol
Surface area26970 Å2
MethodPISA
Unit cell
Length a, b, c (Å)80.228, 86.911, 91.499
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 / MEK kinase kinase 4 / MEKKK 4 / Nck- ...HPK/GCK-like kinase HGK / MAPK/ERK kinase kinase kinase 4 / MEK kinase kinase 4 / MEKKK 4 / Nck-interacting kinase


Mass: 37870.078 Da / Num. of mol.: 2 / Fragment: kinase domain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line: Sf9 / Gene: HGK, KIAA0687, MAP4K4, NIK / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: O95819, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-MES / 2-(N-MORPHOLINO)-ETHANESULFONIC ACID


Mass: 195.237 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H13NO4S / Comment: pH buffer*YM
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-2QT / N-[3-(4-aminoquinazolin-6-yl)-5-fluorophenyl]-2-(pyrrolidin-1-yl)acetamide


Mass: 365.404 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H20FN5O
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 222 / 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: 2.11 Å3/Da / Density % sol: 41.59 %
Crystal growTemperature: 292 K / Method: vapor diffusion, sitting drop / pH: 8.3
Details: 0.2 M potassium citrate pH 8.3, 20% PEG 3350, vapor diffusion, sitting drop, temperature 292K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.9795 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 23, 2011 / Details: mirrors
RadiationMonochromator: DOUBLE CRYSTAL Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.194→91.499 Å / Num. all: 33353 / Num. obs: 33353 / % possible obs: 99.7 % / Redundancy: 6.3 % / Biso Wilson estimate: 49.71 Å2 / Rsym value: 0.059 / Net I/σ(I): 16.1
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allRsym value% possible all
2.19-2.316.40.5231.43069347930.52399.8
2.31-2.456.20.34922819645460.34999.9
2.45-2.626.40.2193.22746043090.21999.8
2.62-2.836.60.145.12642839910.1499.8
2.83-3.16.40.0927.52376137000.09299.8
3.1-3.4760.064102018433410.06499.7
3.47-4.016.40.05111.51902129790.05199.6
4.01-4.915.80.04712.51447925070.04798.8
4.91-6.946.30.04213.61262820100.04299.8
6.94-91.4995.70.03714667111770.03799.1

-
Phasing

PhasingMethod: molecular replacement
Phasing MRPacking: 4

-
Processing

Software
NameVersionClassificationNB
SCALA3.3.16data scaling
PHASERphasing
BUSTER-TNTrefinement
PDB_EXTRACT3.14data extraction
BUSTER2.11.4refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.19→60.32 Å / Cor.coef. Fo:Fc: 0.9413 / Cor.coef. Fo:Fc free: 0.9238 / Occupancy max: 1 / Occupancy min: 0.42 / SU R Cruickshank DPI: 0.269 / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.2401 1677 5.06 %RANDOM
Rwork0.2053 ---
obs0.2071 33138 98.61 %-
Displacement parametersBiso max: 165.46 Å2 / Biso mean: 61.8293 Å2 / Biso min: 27.77 Å2
Baniso -1Baniso -2Baniso -3
1-12.6223 Å20 Å20 Å2
2---13.1065 Å20 Å2
3---0.4842 Å2
Refine analyzeLuzzati coordinate error obs: 0.335 Å
Refinement stepCycle: LAST / Resolution: 2.19→60.32 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4588 0 40 222 4850
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1691SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes112HARMONIC2
X-RAY DIFFRACTIONt_gen_planes703HARMONIC5
X-RAY DIFFRACTIONt_it4761HARMONIC20
X-RAY DIFFRACTIONt_nbd0SEMIHARMONIC5
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion606SEMIHARMONIC5
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_contact5838SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d4761HARMONIC20.009
X-RAY DIFFRACTIONt_angle_deg6439HARMONIC21.05
X-RAY DIFFRACTIONt_omega_torsion3.05
X-RAY DIFFRACTIONt_other_torsion19.55
LS refinement shellResolution: 2.19→2.26 Å / Total num. of bins used: 17
RfactorNum. reflection% reflection
Rfree0.277 134 5 %
Rwork0.2519 2545 -
all0.2532 2679 -
obs--98.61 %

+
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