[English] 日本語
Yorodumi
- PDB-6c3e: CRYSTAL STRUCTURE OF RIP1 KINASE BOUND TO INHIBITOR -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6c3e
TitleCRYSTAL STRUCTURE OF RIP1 KINASE BOUND TO INHIBITOR
ComponentsReceptor-interacting serine/threonine-protein kinase 1
KeywordsTransferase/Transferase Inhibitor / HUMAN RIP1 KINASE / CELL CYCLE / Transferase-Transferase Inhibitor complex
Function / homology
Function and homology information


ripoptosome assembly / positive regulation of miRNA processing / positive regulation of interleukin-6-mediated signaling pathway / ripoptosome assembly involved in necroptotic process / death domain binding / peptidyl-serine autophosphorylation / ripoptosome / Defective RIPK1-mediated regulated necrosis / Microbial modulation of RIPK1-mediated regulated necrosis / TRIF-mediated programmed cell death ...ripoptosome assembly / positive regulation of miRNA processing / positive regulation of interleukin-6-mediated signaling pathway / ripoptosome assembly involved in necroptotic process / death domain binding / peptidyl-serine autophosphorylation / ripoptosome / Defective RIPK1-mediated regulated necrosis / Microbial modulation of RIPK1-mediated regulated necrosis / TRIF-mediated programmed cell death / Regulation by c-FLIP / CASP8 activity is inhibited / Dimerization of procaspase-8 / TLR3-mediated TICAM1-dependent programmed cell death / TNF signaling / programmed necrotic cell death / Caspase activation via Death Receptors in the presence of ligand / SARS-CoV-1-mediated effects on programmed cell death / positive regulation of macrophage differentiation / T cell apoptotic process / JUN kinase kinase kinase activity / necroptotic signaling pathway / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / death-inducing signaling complex / positive regulation of necroptotic process / RIP-mediated NFkB activation via ZBP1 / negative regulation of necroptotic process / positive regulation of tumor necrosis factor-mediated signaling pathway / death receptor binding / positive regulation of programmed cell death / positive regulation of extrinsic apoptotic signaling pathway / positive regulation of programmed necrotic cell death / TNFR1-induced proapoptotic signaling / RIPK1-mediated regulated necrosis / TRP channels / necroptotic process / response to tumor necrosis factor / positive regulation of execution phase of apoptosis / canonical NF-kappaB signal transduction / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / extrinsic apoptotic signaling pathway / tumor necrosis factor-mediated signaling pathway / signaling adaptor activity / negative regulation of canonical NF-kappaB signal transduction / TICAM1, RIP1-mediated IKK complex recruitment / IKK complex recruitment mediated by RIP1 / TNFR1-induced NF-kappa-B signaling pathway / negative regulation of extrinsic apoptotic signaling pathway / positive regulation of interleukin-8 production / positive regulation of JNK cascade / Regulation of TNFR1 signaling / protein catabolic process / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of NF-kappaB transcription factor activity / cellular response to growth factor stimulus / Regulation of necroptotic cell death / cellular response to hydrogen peroxide / positive regulation of inflammatory response / positive regulation of reactive oxygen species metabolic process / positive regulation of tumor necrosis factor production / positive regulation of neuron apoptotic process / Ovarian tumor domain proteases / positive regulation of protein phosphorylation / cellular response to tumor necrosis factor / protein autophosphorylation / amyloid fibril formation / response to oxidative stress / Potential therapeutics for SARS / positive regulation of canonical NF-kappaB signal transduction / receptor complex / non-specific serine/threonine protein kinase / protein kinase activity / endosome membrane / Ub-specific processing proteases / intracellular signal transduction / positive regulation of apoptotic process / inflammatory response / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / ubiquitin protein ligase binding / positive regulation of gene expression / negative regulation of apoptotic process / protein-containing complex binding / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / protein-containing complex / mitochondrion / ATP binding / identical protein binding / plasma membrane / cytosol / cytoplasm
Similarity search - Function
RIP1, Death domain / Death domain profile. / DEATH domain, found in proteins involved in cell death (apoptosis). / Death domain / Death domain / : / Death-like domain superfamily / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Phosphorylase Kinase; domain 1 ...RIP1, Death domain / Death domain profile. / DEATH domain, found in proteins involved in cell death (apoptosis). / Death domain / Death domain / : / Death-like domain superfamily / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Serine/Threonine protein kinases, catalytic domain / 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
2-benzyl-5-nitro-1H-benzimidazole / Receptor-interacting serine/threonine-protein kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.6 Å
AuthorsSaikatendu, K.S. / Yoshikawa, M.
CitationJournal: J. Med. Chem. / Year: 2018
Title: Discovery of 7-Oxo-2,4,5,7-tetrahydro-6 H-pyrazolo[3,4- c]pyridine Derivatives as Potent, Orally Available, and Brain-Penetrating Receptor Interacting Protein 1 (RIP1) Kinase Inhibitors: ...Title: Discovery of 7-Oxo-2,4,5,7-tetrahydro-6 H-pyrazolo[3,4- c]pyridine Derivatives as Potent, Orally Available, and Brain-Penetrating Receptor Interacting Protein 1 (RIP1) Kinase Inhibitors: Analysis of Structure-Kinetic Relationships.
Authors: Yoshikawa, M. / Saitoh, M. / Katoh, T. / Seki, T. / Bigi, S.V. / Shimizu, Y. / Ishii, T. / Okai, T. / Kuno, M. / Hattori, H. / Watanabe, E. / Saikatendu, K.S. / Zou, H. / Nakakariya, M. / ...Authors: Yoshikawa, M. / Saitoh, M. / Katoh, T. / Seki, T. / Bigi, S.V. / Shimizu, Y. / Ishii, T. / Okai, T. / Kuno, M. / Hattori, H. / Watanabe, E. / Saikatendu, K.S. / Zou, H. / Nakakariya, M. / Tatamiya, T. / Nakada, Y. / Yogo, T.
History
DepositionJan 9, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 21, 2018Provider: repository / Type: Initial release
Revision 1.1Apr 4, 2018Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2Mar 13, 2024Group: Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / diffrn_radiation_wavelength
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _diffrn_radiation_wavelength.wavelength

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Receptor-interacting serine/threonine-protein kinase 1
B: Receptor-interacting serine/threonine-protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,6984
Polymers67,1922
Non-polymers5072
Water57632
1
A: Receptor-interacting serine/threonine-protein kinase 1
hetero molecules

B: Receptor-interacting serine/threonine-protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,6984
Polymers67,1922
Non-polymers5072
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_555-x+1/2,-y,z+1/21
Buried area1790 Å2
ΔGint-9 kcal/mol
Surface area23970 Å2
MethodPISA
Unit cell
Length a, b, c (Å)42.262, 95.094, 134.444
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Receptor-interacting serine/threonine-protein kinase 1 / Cell death protein RIP / Receptor-interacting protein 1 / RIP-1 / Serine/threonine-protein kinase RIP


Mass: 33595.762 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RIPK1, RIP, RIP1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q13546, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-EJY / 2-benzyl-5-nitro-1H-benzimidazole


Mass: 253.256 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C14H11N3O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 32 / 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: 2.01 Å3/Da / Density % sol: 38.82 %
Crystal growTemperature: 277 K / Method: vapor diffusion / pH: 7
Details: 0.25 M ammonium iodide, 0.03 M glycyl-glycyl-glycine and polyethylene glycol (PEG) 3350

-
Data collection

DiffractionMean temperature: 277 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.97 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: May 20, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97 Å / Relative weight: 1
ReflectionResolution: 2.6→50 Å / Num. obs: 15973 / % possible obs: 95.7 % / Redundancy: 7.6 % / Net I/σ(I): 12.8
Reflection shellResolution: 2.6→2.66 Å

-
Processing

Software
NameVersionClassification
REFMAC5.8.0049refinement
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.6→44.83 Å / Cor.coef. Fo:Fc: 0.895 / Cor.coef. Fo:Fc free: 0.855 / SU B: 39.409 / SU ML: 0.375 / Cross valid method: THROUGHOUT / ESU R Free: 0.42 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.30665 810 4.8 %RANDOM
Rwork0.259 ---
obs0.26138 15970 96.56 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 44.744 Å2
Baniso -1Baniso -2Baniso -3
1-0.34 Å2-0 Å20 Å2
2--0.03 Å2-0 Å2
3----0.37 Å2
Refinement stepCycle: 1 / Resolution: 2.6→44.83 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4117 0 38 32 4187
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0050.0194249
X-RAY DIFFRACTIONr_bond_other_d0.0010.024155
X-RAY DIFFRACTIONr_angle_refined_deg1.0361.9895720
X-RAY DIFFRACTIONr_angle_other_deg0.74839603
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.7115512
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.35924.633177
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.20715805
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.8041518
X-RAY DIFFRACTIONr_chiral_restr0.0620.2630
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0214650
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02892
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.4581.2092066
X-RAY DIFFRACTIONr_mcbond_other0.4531.2092065
X-RAY DIFFRACTIONr_mcangle_it0.6311.8132572
X-RAY DIFFRACTIONr_mcangle_other0.6311.8132573
X-RAY DIFFRACTIONr_scbond_it0.3661.2262183
X-RAY DIFFRACTIONr_scbond_other0.3661.2262172
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other0.4631.8333137
X-RAY DIFFRACTIONr_long_range_B_refined0.7779.4314699
X-RAY DIFFRACTIONr_long_range_B_other0.7789.4264690
X-RAY DIFFRACTIONr_rigid_bond_restr0.42938404
X-RAY DIFFRACTIONr_sphericity_free20.79514
X-RAY DIFFRACTIONr_sphericity_bonded1.47258336
LS refinement shellResolution: 2.6→2.667 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.437 62 -
Rwork0.294 1120 -
obs--93.36 %
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)
11.75830.0827-0.32343.05590.32311.79640.1016-0.0386-0.07520.09410.02290.0831-0.1331-0.0553-0.12450.25350.00230.01190.38520.02620.01949.8138-3.6097-23.4933
21.45660.04550.86123.4034-1.25993.2959-0.00790.14710.1002-0.38680.0046-0.05030.0407-0.05940.00330.3123-0.02520.01360.38190.02760.123622.031-2.5051-55.3044
31.82442.50580.32637.67690.00220.1489-0.08610.012-0.05630.1254-0.0409-0.4376-0.1056-0.05130.1270.13520.1326-0.13190.3738-0.0250.313511.4304-2.8196-42.2127
41.82880.3016-1.49561.80310.22751.3580.0476-0.04120.1072-0.22460.02360.1188-0.06330.0469-0.07120.2801-0.0135-0.0640.2783-0.0020.023717.2101-6.1868-34.3648
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A9 - 293
2X-RAY DIFFRACTION2B10 - 294
3X-RAY DIFFRACTION3A301
4X-RAY DIFFRACTION3B301
5X-RAY DIFFRACTION4A401 - 420
6X-RAY DIFFRACTION4B401 - 412

+
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