[English] 日本語
Yorodumi
- PDB-4d9u: Rsk2 C-terminal Kinase Domain, (E)-tert-butyl 3-(4-amino-7-(3-hyd... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4d9u
TitleRsk2 C-terminal Kinase Domain, (E)-tert-butyl 3-(4-amino-7-(3-hydroxypropyl)-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-2-cyanoacrylate
ComponentsRibosomal protein S6 kinase alpha-3Ribosome
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / kinase / reversible inhibitor / phosphorylation / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


regulation of translation in response to stress / CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling / ribosomal protein S6 kinase activity / CREB phosphorylation / Gastrin-CREB signalling pathway via PKC and MAPK / RSK activation / toll-like receptor signaling pathway / Recycling pathway of L1 / ERK/MAPK targets / cysteine-type endopeptidase inhibitor activity involved in apoptotic process ...regulation of translation in response to stress / CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling / ribosomal protein S6 kinase activity / CREB phosphorylation / Gastrin-CREB signalling pathway via PKC and MAPK / RSK activation / toll-like receptor signaling pathway / Recycling pathway of L1 / ERK/MAPK targets / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / central nervous system development / skeletal system development / positive regulation of cell differentiation / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / Senescence-Associated Secretory Phenotype (SASP) / chemical synaptic transmission / positive regulation of cell growth / peptidyl-serine phosphorylation / response to lipopolysaccharide / non-specific serine/threonine protein kinase / protein kinase activity / intracellular signal transduction / cell cycle / protein serine kinase activity / protein serine/threonine kinase activity / synapse / nucleolus / negative regulation of apoptotic process / protein kinase binding / magnesium ion binding / signal transduction / positive regulation of transcription by RNA polymerase II / nucleoplasm / ATP binding / cytosol / cytoplasm
Similarity search - Function
Ribosomal protein S6 kinase alpha-3, C-terminal catalytic domain / Ribosomal S6 kinase, N-terminal catalytic domain / Ribosomal protein S6 kinase II / Protein kinase, C-terminal / Protein kinase C terminal domain / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 ...Ribosomal protein S6 kinase alpha-3, C-terminal catalytic domain / Ribosomal S6 kinase, N-terminal catalytic domain / Ribosomal protein S6 kinase II / Protein kinase, C-terminal / Protein kinase C terminal domain / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal 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-0JH / Ribosomal protein S6 kinase alpha-3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.4 Å
AuthorsSerafimova, I.M. / Pufall, M.A. / Krishnan, S. / Duda, K. / Cohen, M.S. / Maglathlin, R.L. / McFarland, J.M. / Miller, R.M. / Frodin, M. / Taunton, J.
CitationJournal: Nat.Chem.Biol. / Year: 2012
Title: Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles.
Authors: Serafimova, I.M. / Pufall, M.A. / Krishnan, S. / Duda, K. / Cohen, M.S. / Maglathlin, R.L. / McFarland, J.M. / Miller, R.M. / Frodin, M. / Taunton, J.
History
DepositionJan 12, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 11, 2012Provider: repository / Type: Initial release
Revision 1.1Apr 25, 2012Group: Database references
Revision 1.2May 16, 2012Group: Database references
Revision 1.3Sep 13, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_conn_type / 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.conn_type_id / _struct_conn.id / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn_type.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: Ribosomal protein S6 kinase alpha-3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,9373
Polymers38,4791
Non-polymers4592
Water55831
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
A: Ribosomal protein S6 kinase alpha-3
hetero molecules

A: Ribosomal protein S6 kinase alpha-3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)77,8756
Polymers76,9582
Non-polymers9174
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation7_465y-1,x+1,-z1
Buried area2540 Å2
ΔGint-40 kcal/mol
Surface area27510 Å2
MethodPISA
Unit cell
Length a, b, c (Å)46.700, 46.700, 293.000
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number92
Space group name H-MP41212

-
Components

#1: Protein Ribosomal protein S6 kinase alpha-3 / Ribosome / S6K-alpha-3 / 90 kDa ribosomal protein S6 kinase 3 / p90-RSK 3 / p90RSK3 / Insulin-stimulated ...S6K-alpha-3 / 90 kDa ribosomal protein S6 kinase 3 / p90-RSK 3 / p90RSK3 / Insulin-stimulated protein kinase 1 / ISPK-1 / MAP kinase-activated protein kinase 1b / MAPK-activated protein kinase 1b / MAPKAP kinase 1b / MAPKAPK-1b / Ribosomal S6 kinase 2 / RSK-2 / pp90RSK2


Mass: 38478.930 Da / Num. of mol.: 1 / Fragment: UNP residues 399-740
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ISPK1, MAPKAPK1B, RPS6KA3, RSK2 / Plasmid: pET46 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)
References: UniProt: P51812, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-0JH / tert-butyl (2S)-3-[4-amino-7-(3-hydroxypropyl)-5-(4-methylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-2-cyanopropanoate / (E)-tert-butyl 3-(4-amino-7-(3-hydroxypropyl)-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-2-cyanoacrylate, bound form


Mass: 435.519 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H29N5O3
#3: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 31 / Source method: isolated from a natural source / Formula: H2O
Nonpolymer detailsTHE UNBOUND FORM OF THE INHIBITOR IS (E)-TERT-BUTYL 3-(4-AMINO-7-(3-HYDROXYPROPYL)-5-P-TOLYL-7H- ...THE UNBOUND FORM OF THE INHIBITOR IS (E)-TERT-BUTYL 3-(4-AMINO-7-(3-HYDROXYPROPYL)-5-P-TOLYL-7H-PYRROLO[2,3-D]PYRIMIDIN-6-YL)-2-CYANOACRYLATE. UPON REACTION WITH PROTEIN, THE DOUBLE BOND BETWEEN C11 AND C12 OPENS UP AND THE LIGAND COVALENTLY BINDS TO CYS436. 0JH REPRESENTS THE BOUND FORM OF THIS INHIBITOR.

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.08 Å3/Da / Density % sol: 40.75 %
Crystal growTemperature: 298 K / Method: hanging drop / pH: 8.5
Details: 100mM Tris, pH 8.5, 25% PEG 3350, hanging drop, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 8.3.1 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Jul 15, 2008
RadiationMonochromator: Double flat crystal, Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.4→46.1 Å / Num. all: 13730 / Num. obs: 13695 / % possible obs: 99.7 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Redundancy: 8 % / Biso Wilson estimate: 59.6 Å2 / Rmerge(I) obs: 0.11 / Rsym value: 0.093 / Net I/σ(I): 14.7
Reflection shellHighest resolution: 2.4 Å / % possible all: 99.7

-
Processing

Software
NameVersionClassificationNB
XSCALEdata scaling
PHENIXdev_613refinement
PDB_EXTRACT3.1data extraction
Blu-Icedata collection
XDSdata reduction
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2QR8

2qr8


Resolution: 2.4→46.1 Å / Occupancy max: 1 / Occupancy min: 1 / FOM work R set: 0.7834 / SU ML: 0.37 / σ(F): 2.04 / Phase error: 26.92 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2756 1370 10.01 %10% random
Rwork0.2044 ---
all0.2114 13730 --
obs0.2114 13693 99.74 %-
Solvent computationShrinkage radii: 0.83 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 46.01 Å2 / ksol: 0.315 e/Å3
Displacement parametersBiso max: 235.42 Å2 / Biso mean: 63.4925 Å2 / Biso min: 20 Å2
Baniso -1Baniso -2Baniso -3
1-6.7937 Å20 Å2-0 Å2
2--6.7937 Å20 Å2
3----13.5874 Å2
Refinement stepCycle: LAST / Resolution: 2.4→46.1 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2403 0 33 31 2467
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0082496
X-RAY DIFFRACTIONf_angle_d1.13384
X-RAY DIFFRACTIONf_chiral_restr0.074372
X-RAY DIFFRACTIONf_plane_restr0.005433
X-RAY DIFFRACTIONf_dihedral_angle_d14.911919
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 10

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.4-2.48580.33011330.28891188132199
2.4858-2.58530.34291310.260911921323100
2.5853-2.70290.31861310.243711781309100
2.7029-2.84540.31871340.234212021336100
2.8454-3.02370.3231350.229212141349100
3.0237-3.25710.34821340.228612081342100
3.2571-3.58470.30121380.209612441382100
3.5847-4.10320.23381380.182712341372100
4.1032-5.16850.24021410.169312761417100
5.1685-46.12640.25481550.200113871542100
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)
11.04020.4101-0.56431.00670.53921.0311-0.036-0.32910.09960.33290.01980.14010.45920.27790.03080.46430.1728-0.01770.4572-0.00160.3229-28.809516.65-15.3407
20.37690.60250.25981.03020.42280.5288-0.3586-0.31370.0424-0.00290.4248-0.41850.15780.5626-0.01390.36630.230.02480.7818-0.0830.3433-9.57722.0996-27.6203
30.1977-0.0896-0.26160.23910.15870.36050.0429-0.2334-0.05340.12810.1697-0.2583-0.00830.59430.15240.2474-0.1357-0.07610.8187-0.23970.39-7.22331.4935-23.7775
40.43510.0915-0.27171.01660.73920.7958-0.0773-0.08460.0108-0.30110.3161-0.0473-0.30360.2489-0.110.4273-0.0854-0.03470.697-0.07270.3716-16.844427.9977-27.916
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resseq 408:587)A408 - 587
2X-RAY DIFFRACTION2chain 'A' and (resseq 588:647)A588 - 647
3X-RAY DIFFRACTION3chain 'A' and (resseq 648:667)A648 - 667
4X-RAY DIFFRACTION4chain 'A' and (resseq 668:714)A668 - 714

+
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