[English] 日本語
Yorodumi
- PDB-7pus: ERK5 in complex with Pyrrole Carboxamide scaffold -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7pus
TitleERK5 in complex with Pyrrole Carboxamide scaffold
ComponentsMitogen-activated protein kinase 7
KeywordsTRANSFERASE / KINASE / INHIBITOR / PYRROLE
Function / homology
Function and homology information


Signalling to ERK5 / negative regulation of response to cytokine stimulus / negative regulation of cyclic-nucleotide phosphodiesterase activity / negative regulation of heterotypic cell-cell adhesion / calcineurin-NFAT signaling cascade / cellular response to laminar fluid shear stress / Gastrin-CREB signalling pathway via PKC and MAPK / ERKs are inactivated / mitogen-activated protein kinase binding / negative regulation of calcineurin-NFAT signaling cascade ...Signalling to ERK5 / negative regulation of response to cytokine stimulus / negative regulation of cyclic-nucleotide phosphodiesterase activity / negative regulation of heterotypic cell-cell adhesion / calcineurin-NFAT signaling cascade / cellular response to laminar fluid shear stress / Gastrin-CREB signalling pathway via PKC and MAPK / ERKs are inactivated / mitogen-activated protein kinase binding / negative regulation of calcineurin-NFAT signaling cascade / ERK/MAPK targets / negative regulation of smooth muscle cell apoptotic process / cAMP-mediated signaling / RET signaling / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / MAP kinase activity / mitogen-activated protein kinase / regulation of angiogenesis / negative regulation of endothelial cell apoptotic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / cellular response to transforming growth factor beta stimulus / positive regulation of protein metabolic process / PML body / cellular response to hydrogen peroxide / cellular response to growth factor stimulus / negative regulation of inflammatory response / MAPK cascade / Senescence-Associated Secretory Phenotype (SASP) / cell differentiation / intracellular signal transduction / cell cycle / phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / signal transduction / positive regulation of transcription by RNA polymerase II / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm
Similarity search - Function
Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / 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
Similarity search - Domain/homology
Chem-86E / Mitogen-activated protein kinase 7
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.59 Å
AuthorsTucker, J.A. / Martin, M.P. / Endicott, J.A. / Noble, M.E.N.
Funding support United Kingdom, 1items
OrganizationGrant numberCountry
Medical Research Council (MRC, United Kingdom) United Kingdom
CitationJournal: J.Med.Chem. / Year: 2022
Title: Parallel Optimization of Potency and Pharmacokinetics Leading to the Discovery of a Pyrrole Carboxamide ERK5 Kinase Domain Inhibitor.
Authors: Miller, D.C. / Reuillon, T. / Molyneux, L. / Blackburn, T. / Cook, S.J. / Edwards, N. / Endicott, J.A. / Golding, B.T. / Griffin, R.J. / Hardcastle, I. / Harnor, S.J. / Heptinstall, A. / ...Authors: Miller, D.C. / Reuillon, T. / Molyneux, L. / Blackburn, T. / Cook, S.J. / Edwards, N. / Endicott, J.A. / Golding, B.T. / Griffin, R.J. / Hardcastle, I. / Harnor, S.J. / Heptinstall, A. / Lochhead, P. / Martin, M.P. / Martin, N.C. / Myers, S. / Newell, D.R. / Noble, R.A. / Phillips, N. / Rigoreau, L. / Thomas, H. / Tucker, J.A. / Wang, L.Z. / Waring, M.J. / Wong, A.C. / Wedge, S.R. / Noble, M.E.M. / Cano, C.
History
DepositionSep 30, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0May 11, 2022Provider: repository / Type: Initial release
Revision 1.1May 25, 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 1.2Jan 31, 2024Group: Data collection / Derived calculations / Refinement description
Category: atom_type / chem_comp_atom ...atom_type / chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Item: _atom_type.pdbx_N_electrons / _atom_type.pdbx_scat_Z

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
AAA: Mitogen-activated protein kinase 7
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,4382
Polymers41,0571
Non-polymers3811
Water23413
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)91.671, 91.671, 113.810
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number92
Space group name H-MP41212

-
Components

#1: Protein Mitogen-activated protein kinase 7 / MAPK 7 / Big MAP kinase 1 / BMK-1 / Extracellular signal-regulated kinase 5 / ERK-5


Mass: 41057.234 Da / Num. of mol.: 1 / Fragment: UNP residues 46-402
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK7, BMK1, ERK5, PRKM7 / Plasmid: PFASTBAC HT A / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q13164, mitogen-activated protein kinase
#2: Chemical ChemComp-86E / 4-[3,6-bis(chloranyl)-2-fluoranyl-phenyl]carbonyl-~{N}-(1-methylpyrazol-4-yl)-1~{H}-pyrrole-2-carboxamide


Mass: 381.189 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H11Cl2FN4O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 13 / 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: 2.91 Å3/Da / Density % sol: 57.76 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / Details: 5 % (V/V) PEG 6000, 0.1 M MES (PH 6.0), 5 MM DTT

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I24 / Wavelength: 0.9795 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: May 10, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.59→71.49 Å / Num. obs: 15740 / % possible obs: 100 % / Redundancy: 13.9 % / CC1/2: 0.986 / Rpim(I) all: 0.145 / Rrim(I) all: 0.398 / Net I/σ(I): 5.7
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) all% possible allMean I/σ(I) obs
2.59-71.39110.114157400.9830.0450.123100
2.59-2.7114.24.12119000.4321.6184.431.1

-
Processing

Software
NameVersionClassification
REFMAC5.8.0258refinement
REFMAC5.8.0258refinement
DIALSdata reduction
pointlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5O7I

5o7i


Resolution: 2.59→71.49 Å / Cor.coef. Fo:Fc: 0.942 / Cor.coef. Fo:Fc free: 0.897 / SU B: 14.431 / SU ML: 0.282 / Cross valid method: FREE R-VALUE / ESU R: 0.496 / ESU R Free: 0.325
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2853 790 5.035 %
Rwork0.2192 14901 -
all0.222 --
obs-15691 100 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 59.589 Å2
Baniso -1Baniso -2Baniso -3
1-1.55 Å20 Å2-0 Å2
2--1.55 Å20 Å2
3----3.1 Å2
Refinement stepCycle: LAST / Resolution: 2.59→71.49 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2713 0 25 13 2751
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0122842
X-RAY DIFFRACTIONr_angle_refined_deg1.6721.643865
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.2055345
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.60320.248161
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.83115470
X-RAY DIFFRACTIONr_dihedral_angle_4_deg22.1491528
X-RAY DIFFRACTIONr_chiral_restr0.1120.2363
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.022230
X-RAY DIFFRACTIONr_nbd_refined0.2080.21214
X-RAY DIFFRACTIONr_nbtor_refined0.3130.21934
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1190.259
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.2180.234
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.2680.22
X-RAY DIFFRACTIONr_mcbond_it6.0155.9321374
X-RAY DIFFRACTIONr_mcangle_it8.8918.9031721
X-RAY DIFFRACTIONr_scbond_it7.4216.0561468
X-RAY DIFFRACTIONr_scangle_it10.9018.9892144
X-RAY DIFFRACTIONr_lrange_it15.093109.59911909
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.59-2.6570.386670.3411078X-RAY DIFFRACTION100
2.657-2.730.374530.3431058X-RAY DIFFRACTION100
2.73-2.8090.363520.3191016X-RAY DIFFRACTION100
2.809-2.8960.385450.289991X-RAY DIFFRACTION100
2.896-2.9910.387520.27960X-RAY DIFFRACTION100
2.991-3.0950.332470.247935X-RAY DIFFRACTION100
3.095-3.2120.342560.232903X-RAY DIFFRACTION100
3.212-3.3430.271390.245880X-RAY DIFFRACTION100
3.343-3.4920.311500.222839X-RAY DIFFRACTION100
3.492-3.6620.31410.207809X-RAY DIFFRACTION100
3.662-3.860.223380.183762X-RAY DIFFRACTION100
3.86-4.0940.221400.185731X-RAY DIFFRACTION100
4.094-4.3760.183370.179690X-RAY DIFFRACTION100
4.376-4.7260.195380.171637X-RAY DIFFRACTION100
4.726-5.1760.343320.187597X-RAY DIFFRACTION100
5.176-5.7860.255290.207547X-RAY DIFFRACTION100
5.786-6.6780.296320.252485X-RAY DIFFRACTION100
6.678-8.1720.315190.189427X-RAY DIFFRACTION100
8.172-11.5270.263130.161346X-RAY DIFFRACTION100
11.527-71.490.303100.297210X-RAY DIFFRACTION100

+
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