[English] 日本語
Yorodumi
- PDB-9d75: Human p38alpha MAP Kinase in complex with 1-(Cyclohexylmethyl)-1H... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9d75
TitleHuman p38alpha MAP Kinase in complex with 1-(Cyclohexylmethyl)-1H-indazole derivative; OSF346
ComponentsMitogen-activated protein kinase 14
KeywordsTRANSFERASE / P38 / KINASE / INHIBITOR / COMPLEX
Function / homology
Function and homology information


stress-activated protein kinase signaling cascade / positive regulation of cyclase activity / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / regulation of synaptic membrane adhesion / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / CD163 mediating an anti-inflammatory response / 3'-UTR-mediated mRNA stabilization / KSRP (KHSRP) binds and destabilizes mRNA / positive regulation of myoblast fusion ...stress-activated protein kinase signaling cascade / positive regulation of cyclase activity / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / regulation of synaptic membrane adhesion / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / CD163 mediating an anti-inflammatory response / 3'-UTR-mediated mRNA stabilization / KSRP (KHSRP) binds and destabilizes mRNA / positive regulation of myoblast fusion / cellular response to UV-B / cartilage condensation / mitogen-activated protein kinase p38 binding / positive regulation of muscle cell differentiation / Platelet sensitization by LDL / Myogenesis / positive regulation of myotube differentiation / NFAT protein binding / regulation of cytokine production involved in inflammatory response / Activation of the AP-1 family of transcription factors / D-glucose import / p38MAPK cascade / ERK/MAPK targets / fatty acid oxidation / response to dietary excess / cellular response to lipoteichoic acid / response to muramyl dipeptide / MAP kinase kinase activity / Regulation of MITF-M-dependent genes involved in pigmentation / signal transduction in response to DNA damage / MAP kinase activity / regulation of ossification / cellular response to vascular endothelial growth factor stimulus / RHO GTPases Activate NADPH Oxidases / mitogen-activated protein kinase / chondrocyte differentiation / vascular endothelial growth factor receptor signaling pathway / negative regulation of hippo signaling / positive regulation of myoblast differentiation / stress-activated MAPK cascade / skeletal muscle tissue development / positive regulation of cardiac muscle cell proliferation / p38MAPK events / positive regulation of brown fat cell differentiation / response to muscle stretch / striated muscle cell differentiation / positive regulation of interleukin-12 production / positive regulation of erythrocyte differentiation / osteoclast differentiation / lipopolysaccharide-mediated signaling pathway / DNA damage checkpoint signaling / placenta development / tumor necrosis factor-mediated signaling pathway / positive regulation of D-glucose import / cellular response to ionizing radiation / activated TAK1 mediates p38 MAPK activation / stem cell differentiation / negative regulation of inflammatory response to antigenic stimulus / negative regulation of canonical Wnt signaling pathway / NOD1/2 Signaling Pathway / response to insulin / bone development / cellular response to virus / platelet activation / positive regulation of protein import into nucleus / VEGFA-VEGFR2 Pathway / glucose metabolic process / positive regulation of reactive oxygen species metabolic process / cell morphogenesis / chemotaxis / spindle pole / osteoblast differentiation / cellular senescence / ADP signalling through P2Y purinoceptor 1 / MAPK cascade / cellular response to lipopolysaccharide / angiogenesis / secretory granule lumen / protein phosphatase binding / Oxidative Stress Induced Senescence / Regulation of TP53 Activity through Phosphorylation / ficolin-1-rich granule lumen / transcription by RNA polymerase II / cell surface receptor signaling pathway / intracellular signal transduction / nuclear speck / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / Neutrophil degranulation / positive regulation of gene expression / regulation of transcription by RNA polymerase II / glutamatergic synapse / enzyme binding / signal transduction / positive regulation of transcription by RNA polymerase II / mitochondrion / extracellular region / nucleoplasm / ATP binding
Similarity search - Function
Mitogen-activated protein kinase 14 / Mitogen-activated protein (MAP) kinase p38-like / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase 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. ...Mitogen-activated protein kinase 14 / Mitogen-activated protein (MAP) kinase p38-like / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase 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
: / 4-[3-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL]PYRIDINE / Mitogen-activated protein kinase 14
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.13 Å
AuthorsBrunzelle, J.S. / Shuvalova, L. / Benetik, S.F. / Roy, S.M. / Watterson, D.M. / Gobec, S.
Funding support1items
OrganizationGrant numberCountry
Other private
CitationJournal: J.Med.Chem. / Year: 2025
Title: Targeting Neuroinflammation and Cognitive Decline: First-in-Class Dual Butyrylcholinesterase and p38 alpha Mitogen-Activated Protein Kinase Inhibitors.
Authors: Ferjancic Benetik, S. / Proj, M. / Knez, D. / Kosak, U. / Meden, A. / Krajsek, K. / Pislar, A. / Horvat, S. / Svajger, U. / Tesic, N. / Pulkrabkova, L. / Soukup, O. / Skarka, A. / Andrys, R. ...Authors: Ferjancic Benetik, S. / Proj, M. / Knez, D. / Kosak, U. / Meden, A. / Krajsek, K. / Pislar, A. / Horvat, S. / Svajger, U. / Tesic, N. / Pulkrabkova, L. / Soukup, O. / Skarka, A. / Andrys, R. / Brazzolotto, X. / Igert, A. / Nachon, F. / Dias, J. / Detka, J. / Gdula-Argasinska, J. / Wyska, E. / Szafarz, M. / Manik, A. / Plachtij, N. / Musilek, K. / Salat, K. / Obreza, A. / Gobec, S.
History
DepositionAug 16, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 24, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Mitogen-activated protein kinase 14
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,4413
Polymers39,7481
Non-polymers6942
Water1,17165
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)65.906, 75.480, 78.923
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

#1: Protein Mitogen-activated protein kinase 14 / MAP kinase 14 / MAPK 14 / Cytokine suppressive anti-inflammatory drug-binding protein / CSAID- ...MAP kinase 14 / MAPK 14 / Cytokine suppressive anti-inflammatory drug-binding protein / CSAID-binding protein / CSBP / MAP kinase MXI2 / MAX-interacting protein 2 / Mitogen-activated protein kinase p38 alpha / MAP kinase p38 alpha / Stress-activated protein kinase 2a / SAPK2a


Mass: 39747.539 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK14, CSBP, CSBP1, CSBP2, CSPB1, MXI2, SAPK2A / Production host: Escherichia coli (E. coli)
References: UniProt: Q16539, mitogen-activated protein kinase
#2: Chemical ChemComp-A1A2L / 1-(cyclohexylmethyl)-5-[(2,4-difluorophenyl)methyl]-N-[2-(dimethylamino)ethyl]-1H-indazole-6-carboxamide


Mass: 454.555 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H32F2N4O / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-GG5 / 4-[3-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL]PYRIDINE


Mass: 239.248 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H10FN3
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 65 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.47 Å3/Da / Density % sol: 50.19 %
Crystal growTemperature: 295 K / Method: vapor diffusion, sitting drop / pH: 5.5
Details: 0.1M Ammonium Acetate, 0.1M BisTris (pH 5.5), 20% PEG 10,000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID30B / Wavelength: 0.8731 Å
DetectorType: DECTRIS EIGER2 X 9M / Detector: PIXEL / Date: Jul 14, 2023 / Details: Vertical CRL / Horizontal Eliptical mirror
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.8731 Å / Relative weight: 1
ReflectionResolution: 2.13→42.02 Å / Num. obs: 22682 / % possible obs: 100 % / Redundancy: 13.3 % / Biso Wilson estimate: 47.24 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.109 / Rpim(I) all: 0.044 / Rrim(I) all: 0.118 / Χ2: 0.98 / Net I/σ(I): 14.3
Reflection shellResolution: 2.13→2.2 Å / Redundancy: 13.8 % / Rmerge(I) obs: 2.17 / Mean I/σ(I) obs: 1.3 / Num. unique obs: 2178 / CC1/2: 0.653 / Rpim(I) all: 0.865 / Rrim(I) all: 2.399 / Χ2: 0.87 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
Aimless0.7.7data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.13→42.02 Å / SU ML: 0.2512 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 27.5307
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.236 1155 5.1 %
Rwork0.2065 21473 -
obs0.2081 22628 99.97 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 58.21 Å2
Refinement stepCycle: LAST / Resolution: 2.13→42.02 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2708 0 51 65 2824
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00372878
X-RAY DIFFRACTIONf_angle_d0.66463915
X-RAY DIFFRACTIONf_chiral_restr0.0409429
X-RAY DIFFRACTIONf_plane_restr0.0075511
X-RAY DIFFRACTIONf_dihedral_angle_d6.6587409
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.13-2.230.33051360.29222650X-RAY DIFFRACTION99.93
2.23-2.340.3151360.26042639X-RAY DIFFRACTION99.96
2.34-2.490.23511310.25442642X-RAY DIFFRACTION100
2.49-2.680.30631330.25452662X-RAY DIFFRACTION100
2.68-2.950.27591450.22582676X-RAY DIFFRACTION100
2.95-3.380.29311480.2362673X-RAY DIFFRACTION100
3.38-4.260.19671530.18152712X-RAY DIFFRACTION100
4.26-42.020.20571730.17812819X-RAY DIFFRACTION99.9
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.98603895255-0.861659551842-0.574880289271.29627921758-0.5141461230081.05543545096-0.189886585676-0.3002335619960.1045859324290.3975935367410.2174242456470.775632786663-0.665911911470.234868525413-0.0001645339620650.6583455710080.03611066583080.1205827216560.68088038790.140828500040.869680563035-17.22755193633.1168246931222.4043717367
20.864450573736-0.08358474551210.3754550851040.290744934875-0.2652160271880.444136970002-0.03114055574670.661970879677-1.064332989280.1059609572430.2202708877081.181219047220.396733045091-0.363126337908-0.002162691760040.4985150284330.03547750557640.08530013652440.4658891478350.1117438664050.75557522453-11.6539253474-5.9374664695621.656209882
32.373410546940.1719801811350.005308545599891.51370139724-1.123699709652.179794520220.175448033080.026372938228-0.09869881157370.172079881608-0.099142898280.129621810974-0.219491366269-0.005445497876510.0002851739134830.3686173171440.003451352583640.01204622226020.3087173607340.006681627571920.287794376933-5.116733059586.2954653621710.8056193416
41.823501749490.249187969897-1.213515395621.00531620046-1.943649855792.50666907969-0.1226400893490.36136415878-0.05876650081910.2597322849640.2612674651360.648137526417-0.476634633163-0.467710355783-0.01440561824440.4740867624470.0386986234804-0.03713263529790.4585734626260.0768760146380.586850890047-11.67390127393.8095376916715.5530296415
50.3028991801310.7965654697370.2464404972722.427723866630.6330197561160.183883582253-0.231441689659-0.04844802570930.0471861990750.3929797714140.236996393237-0.592988648671-0.404787884117-0.001131447812140.200048634811.10342807371-0.05143966244930.1303978273981.292358558850.2122513856040.67003714658511.1885419579-3.4186288422734.0773420647
61.875078675430.2190789485530.7405199930291.55193040077-0.09392791888361.422547226450.0963651617622-0.0263764487859-0.419435480603-0.0781342010347-0.1437497373150.006468335933320.252118800697-0.100529314054-0.0003206793314530.4029988427590.01020253899780.00589933501820.3916133988910.07061841012560.45039329724110.0307939424-3.6240214036417.4118242906
72.21943723235-1.83764248268-1.84437653163.156338997260.5750723724482.18105029377-0.363757365793-0.5707369542140.2375642168711.74488789059-0.1159831115510.713430859074-1.41551665769-0.732056875859-0.1511213751491.01512462042-0.0809686137736-0.1301694887050.6557478981870.06309321414990.6453679711117.382984181719.4935675904419.1818397848
81.875495156990.82428625447-0.5753334265331.246772182031.06410914281.241636659070.0966330302735-0.1013330798440.3257819340180.103045320291-0.06930894201620.148396563755-0.189733274332-0.0931044525851-0.0001476088285710.429227789098-0.04398168435530.01690580375010.4285198752050.05792884119330.40626160858318.468253635810.579172325820.0930542879
92.723910763680.2657424338580.3683277415832.22908228425-0.194739128341.26663883460.1552441347-0.206341973036-0.2023234425560.0535047573671-0.222296192346-0.614408574755-0.1157247065830.3996005378450.0007800056835410.482246602411-0.01469608831590.0303819589120.5731602538040.09612378907820.46130998333625.57159814214.5623967936115.638963625
101.60793808363-0.35463066271-1.119463281650.919444908323-0.6058362157013.129378603540.2418390920130.3237712065220.243513623347-0.433189792565-0.184040384550.243093545059-0.0139536906348-0.1412178218170.0002527307997260.4749279990090.0483591798676-0.1216015084180.5409148539490.01948480444560.458496521267-8.171763019497.904675150072.34774802563
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION / Auth asym-ID: A / Label asym-ID: A

IDRefine TLS-IDSelection detailsAuth seq-IDLabel seq-ID
11chain A and resid 5:365 - 361 - 32
22chain A and resid 37:5237 - 5233 - 48
33chain A and resid 53:9053 - 9049 - 86
44chain A and resid 91:11491 - 11487 - 110
55chain A and resid 115:122115 - 122111 - 118
66chain A and resid 123:167123 - 167119 - 163
77chain A and resid 168:186168 - 186164 - 168
88chain A and resid 187:235187 - 235169 - 217
99chain A and resid 236:323236 - 323218 - 305
1010chain A and resid 324:353324 - 353306 - 335

+
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