[English] 日本語
Yorodumi
- PDB-6ocq: Crystal structure of RIP1 kinase in complex with a pyrrolidine -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ocq
TitleCrystal structure of RIP1 kinase in complex with a pyrrolidine
ComponentsReceptor-interacting serine/threonine-protein kinase 1
KeywordsSIGNALING PROTEIN/INHIBITOR / inhibitor / SIGNALING PROTEIN / SIGNALING PROTEIN-INHIBITOR complex
Function / homology
Function and homology information


regulation of ATP:ADP antiporter activity / ripoptosome assembly / positive regulation of miRNA processing / positive regulation of interleukin-6-mediated signaling pathway / ripoptosome assembly involved in necroptotic process / death domain binding / ripoptosome / Defective RIPK1-mediated regulated necrosis / TRIF-mediated programmed cell death / TLR3-mediated TICAM1-dependent programmed cell death ...regulation of ATP:ADP antiporter activity / ripoptosome assembly / positive regulation of miRNA processing / positive regulation of interleukin-6-mediated signaling pathway / ripoptosome assembly involved in necroptotic process / death domain binding / ripoptosome / Defective RIPK1-mediated regulated necrosis / TRIF-mediated programmed cell death / TLR3-mediated TICAM1-dependent programmed cell death / Microbial modulation of RIPK1-mediated regulated necrosis / Regulation by c-FLIP / CASP8 activity is inhibited / Dimerization of procaspase-8 / 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 / necroptotic signaling pathway / positive regulation of macrophage differentiation / T cell apoptotic process / JUN kinase kinase kinase activity / peptidyl-serine autophosphorylation / positive regulation of necroptotic process / positive regulation of tumor necrosis factor-mediated signaling pathway / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / RIP-mediated NFkB activation via ZBP1 / death-inducing signaling complex / negative regulation of necroptotic process / death receptor binding / positive regulation of extrinsic apoptotic signaling pathway / positive regulation of programmed cell death / positive regulation of programmed necrotic cell death / TRP channels / TNFR1-induced proapoptotic signaling / RIPK1-mediated regulated necrosis / necroptotic process / positive regulation of execution phase of apoptosis / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / response to tumor necrosis factor / negative regulation of canonical NF-kappaB signal transduction / signaling adaptor activity / tumor necrosis factor-mediated signaling pathway / extrinsic apoptotic signaling pathway / TICAM1, RIP1-mediated IKK complex recruitment / IKK complex recruitment mediated by RIP1 / TNFR1-induced NF-kappa-B signaling pathway / positive regulation of interleukin-8 production / negative regulation of extrinsic apoptotic signaling pathway / positive regulation of JNK cascade / Regulation of TNFR1 signaling / protein catabolic process / cellular response to growth factor stimulus / Regulation of necroptotic cell death / cellular response to hydrogen peroxide / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of neuron apoptotic process / positive regulation of reactive oxygen species metabolic process / positive regulation of tumor necrosis factor production / Ovarian tumor domain proteases / cellular response to tumor necrosis factor / positive regulation of NF-kappaB transcription factor activity / positive regulation of canonical NF-kappaB signal transduction / response to oxidative stress / protein autophosphorylation / amyloid fibril formation / Potential therapeutics for SARS / receptor complex / non-specific serine/threonine protein kinase / protein kinase activity / endosome membrane / intracellular signal transduction / Ub-specific processing proteases / inflammatory response / positive regulation of apoptotic process / positive regulation of protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / ubiquitin protein ligase binding / protein-containing complex binding / positive regulation of gene expression / negative regulation of apoptotic process / apoptotic process / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / protein-containing complex / mitochondrion / ATP binding / identical protein binding / plasma membrane / cytosol
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 / Transferase(Phosphotransferase) 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 / 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. / 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
Chem-M5J / Receptor-interacting serine/threonine-protein kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.793 Å
AuthorsThorpe, J.H. / Harris, P.A.
CitationJournal: J.Med.Chem. / Year: 2019
Title: Discovery and Lead-Optimization of 4,5-Dihydropyrazoles as Mono-Kinase Selective, Orally Bioavailable and Efficacious Inhibitors of Receptor Interacting Protein 1 (RIP1) Kinase.
Authors: Harris, P.A. / Faucher, N. / George, N. / Eidam, P.M. / King, B.W. / White, G.V. / Anderson, N.A. / Bandyopadhyay, D. / Beal, A.M. / Beneton, V. / Berger, S.B. / Campobasso, N. / Campos, S. ...Authors: Harris, P.A. / Faucher, N. / George, N. / Eidam, P.M. / King, B.W. / White, G.V. / Anderson, N.A. / Bandyopadhyay, D. / Beal, A.M. / Beneton, V. / Berger, S.B. / Campobasso, N. / Campos, S. / Capriotti, C.A. / Cox, J.A. / Daugan, A. / Donche, F. / Fouchet, M.H. / Finger, J.N. / Geddes, B. / Gough, P.J. / Grondin, P. / Hoffman, B.L. / Hoffman, S.J. / Hutchinson, S.E. / Jeong, J.U. / Jigorel, E. / Lamoureux, P. / Leister, L.K. / Lich, J.D. / Mahajan, M.K. / Meslamani, J. / Mosley, J.E. / Nagilla, R. / Nassau, P.M. / Ng, S.L. / Ouellette, M.T. / Pasikanti, K.K. / Potvain, F. / Reilly, M.A. / Rivera, E.J. / Sautet, S. / Schaeffer, M.C. / Sehon, C.A. / Sun, H. / Thorpe, J.H. / Totoritis, R.D. / Ward, P. / Wellaway, N. / Wisnoski, D.D. / Woolven, J.M. / Bertin, J. / Marquis, R.W.
History
DepositionMar 25, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 8, 2019Provider: repository / Type: Initial release
Revision 1.1Jun 5, 2019Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.name
Revision 1.2Mar 13, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
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)69,8856
Polymers69,1942
Non-polymers6914
Water724
1
A: Receptor-interacting serine/threonine-protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,9423
Polymers34,5971
Non-polymers3452
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Receptor-interacting serine/threonine-protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,9423
Polymers34,5971
Non-polymers3452
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)47.297, 95.117, 127.240
Angle α, β, γ (deg.)90.000, 90.000, 90.000
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


Mass: 34596.891 Da / Num. of mol.: 2 / Fragment: N-terminal residues 1-294 / Mutation: C34A, C127A, C233A, C240A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RIPK1, RIP, RIP1
Production host: Spodoptera aff. frugiperda 2 RZ-2014 (butterflies/moths)
References: UniProt: Q13546, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-M5J / 1-[(2S)-2-(3-fluorophenyl)pyrrolidin-1-yl]-2,2-dimethylpropan-1-one


Mass: 249.324 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C15H20FNO / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 4 / 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: 2.07 Å3/Da / Density % sol: 40.53 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 24 % PEG 4000, 0.1 M ammonium acetate, 0.1 M HEPES pH 7.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 1.07 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Oct 3, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.07 Å / Relative weight: 1
ReflectionResolution: 2.79→95.12 Å / Num. obs: 14805 / % possible obs: 99.7 % / Redundancy: 4.7 % / Biso Wilson estimate: 70.52 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.06 / Rpim(I) all: 0.03 / Rrim(I) all: 0.068 / Net I/σ(I): 17 / Num. measured all: 70273
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
2.79-2.944.90.5341039021130.8140.2660.5982.5100
8.83-95.1240.02420825260.9990.0130.02842.296.7

-
Processing

Software
NameVersionClassification
Aimless0.5.32data scaling
PHENIX1.11.1_2575refinement
PDB_EXTRACT3.24data extraction
XDSdata reduction
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.793→76.183 Å / SU ML: 0.41 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 29.79
RfactorNum. reflection% reflection
Rfree0.2681 682 4.62 %
Rwork0.2028 --
obs0.2059 14754 99.33 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 134.51 Å2 / Biso mean: 72.2768 Å2 / Biso min: 32.78 Å2
Refinement stepCycle: final / Resolution: 2.793→76.183 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4167 0 46 4 4217
Biso mean--69.24 48.48 -
Num. residues----536
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0094315
X-RAY DIFFRACTIONf_angle_d1.2115843
X-RAY DIFFRACTIONf_chiral_restr0.059654
X-RAY DIFFRACTIONf_plane_restr0.006747
X-RAY DIFFRACTIONf_dihedral_angle_d4.6683615
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 5

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.7928-3.00850.38661310.270327362867100
3.0085-3.31120.35321410.248227832924100
3.3112-3.79030.31361350.209827882923100
3.7903-4.77530.22951340.18312828296299
4.7753-76.21180.23431410.19012937307898

+
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