[English] 日本語
Yorodumi
- PDB-8tbj: Tricomplex of RMC-7977, KRAS G12A, and CypA -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8tbj
TitleTricomplex of RMC-7977, KRAS G12A, and CypA
Components
  • GTPase KRas
  • Peptidyl-prolyl cis-trans isomerase A
KeywordsHYDROLASE/INHIBITOR / inhibitor / complex / small GTPase / cancer / tricomplex / HYDROLASE-INHIBITOR complex
Function / homology
Function and homology information


negative regulation of protein K48-linked ubiquitination / regulation of apoptotic signaling pathway / cell adhesion molecule production / lipid droplet organization / negative regulation of viral life cycle / heparan sulfate binding / regulation of viral genome replication / leukocyte chemotaxis / virion binding / negative regulation of stress-activated MAPK cascade ...negative regulation of protein K48-linked ubiquitination / regulation of apoptotic signaling pathway / cell adhesion molecule production / lipid droplet organization / negative regulation of viral life cycle / heparan sulfate binding / regulation of viral genome replication / leukocyte chemotaxis / virion binding / negative regulation of stress-activated MAPK cascade / endothelial cell activation / Basigin interactions / response to mineralocorticoid / GMP binding / forebrain astrocyte development / protein peptidyl-prolyl isomerization / LRR domain binding / cyclosporin A binding / regulation of synaptic transmission, GABAergic / Minus-strand DNA synthesis / Plus-strand DNA synthesis / negative regulation of epithelial cell differentiation / response to isolation stress / Uncoating of the HIV Virion / response to gravity / epithelial tube branching involved in lung morphogenesis / Early Phase of HIV Life Cycle / type I pneumocyte differentiation / Integration of provirus / Rac protein signal transduction / negative regulation of protein phosphorylation / APOBEC3G mediated resistance to HIV-1 infection / positive regulation of Rac protein signal transduction / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants / Activation of RAS in B cells / viral release from host cell / myoblast proliferation / skeletal muscle cell differentiation / RAS signaling downstream of NF1 loss-of-function variants / RUNX3 regulates p14-ARF / Calcineurin activates NFAT / positive regulation of glial cell proliferation / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / SHC1 events in ERBB4 signaling / activation of protein kinase B activity / Binding and entry of HIV virion / cardiac muscle cell proliferation / Signalling to RAS / Activated NTRK2 signals through FRS2 and FRS3 / SHC-related events triggered by IGF1R / Estrogen-stimulated signaling through PRKCZ / positive regulation of viral genome replication / glial cell proliferation / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / SHC-mediated cascade:FGFR2 / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR4 / negative regulation of protein kinase activity / Erythropoietin activates RAS / SHC-mediated cascade:FGFR1 / Signaling by FGFR4 in disease / Signaling by CSF3 (G-CSF) / FRS-mediated FGFR3 signaling / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / p38MAPK events / FRS-mediated FGFR1 signaling / Signaling by FGFR3 in disease / protein-membrane adaptor activity / Tie2 Signaling / striated muscle cell differentiation / Signaling by FGFR2 in disease / neutrophil chemotaxis / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / Signaling by FLT3 fusion proteins / FLT3 Signaling / Signaling by FGFR1 in disease / EGFR Transactivation by Gastrin / NCAM signaling for neurite out-growth / homeostasis of number of cells within a tissue / CD209 (DC-SIGN) signaling / GRB2 events in ERBB2 signaling / Downstream signal transduction / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / Insulin receptor signalling cascade / Ras activation upon Ca2+ influx through NMDA receptor / SHC1 events in ERBB2 signaling / response to glucocorticoid / Constitutive Signaling by Overexpressed ERBB2 / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / VEGFR2 mediated cell proliferation
Similarity search - Function
Cyclophilin-type peptidyl-prolyl cis-trans isomerase / Cyclophilin-type peptidyl-prolyl cis-trans isomerase, conserved site / Cyclophilin-type peptidyl-prolyl cis-trans isomerase signature. / Cyclophilin-type peptidyl-prolyl cis-trans isomerase domain profile. / Cyclophilin-type peptidyl-prolyl cis-trans isomerase domain / Cyclophilin type peptidyl-prolyl cis-trans isomerase/CLD / Cyclophilin-like domain superfamily / Small GTPase, Ras-type / Small GTPase Ras domain profile. / Ran (Ras-related nuclear proteins) /TC4 subfamily of small GTPases ...Cyclophilin-type peptidyl-prolyl cis-trans isomerase / Cyclophilin-type peptidyl-prolyl cis-trans isomerase, conserved site / Cyclophilin-type peptidyl-prolyl cis-trans isomerase signature. / Cyclophilin-type peptidyl-prolyl cis-trans isomerase domain profile. / Cyclophilin-type peptidyl-prolyl cis-trans isomerase domain / Cyclophilin type peptidyl-prolyl cis-trans isomerase/CLD / Cyclophilin-like domain superfamily / Small GTPase, Ras-type / Small GTPase Ras domain profile. / Ran (Ras-related nuclear proteins) /TC4 subfamily of small GTPases / Rho (Ras homology) subfamily of Ras-like small GTPases / Ras subfamily of RAS small GTPases / Small GTPase / Ras family / Rab subfamily of small GTPases / Small GTP-binding protein domain / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER / : / GTPase KRas / Peptidyl-prolyl cis-trans isomerase A
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.45 Å
AuthorsTomlinson, A.C.A. / Chen, A. / Knox, J.E. / Yano, J.K.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Nature / Year: 2024
Title: Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy.
Authors: Holderfield, M. / Lee, B.J. / Jiang, J. / Tomlinson, A. / Seamon, K.J. / Mira, A. / Patrucco, E. / Goodhart, G. / Dilly, J. / Gindin, Y. / Dinglasan, N. / Wang, Y. / Lai, L.P. / Cai, S. / ...Authors: Holderfield, M. / Lee, B.J. / Jiang, J. / Tomlinson, A. / Seamon, K.J. / Mira, A. / Patrucco, E. / Goodhart, G. / Dilly, J. / Gindin, Y. / Dinglasan, N. / Wang, Y. / Lai, L.P. / Cai, S. / Jiang, L. / Nasholm, N. / Shifrin, N. / Blaj, C. / Shah, H. / Evans, J.W. / Montazer, N. / Lai, O. / Shi, J. / Ahler, E. / Quintana, E. / Chang, S. / Salvador, A. / Marquez, A. / Cregg, J. / Liu, Y. / Milin, A. / Chen, A. / Ziv, T.B. / Parsons, D. / Knox, J.E. / Klomp, J.E. / Roth, J. / Rees, M. / Ronan, M. / Cuevas-Navarro, A. / Hu, F. / Lito, P. / Santamaria, D. / Aguirre, A.J. / Waters, A.M. / Der, C.J. / Ambrogio, C. / Wang, Z. / Gill, A.L. / Koltun, E.S. / Smith, J.A.M. / Wildes, D. / Singh, M.
History
DepositionJun 28, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 7, 2024Provider: repository / Type: Initial release
Revision 1.1Apr 24, 2024Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Jun 5, 2024Group: 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: GTPase KRas
B: GTPase KRas
C: Peptidyl-prolyl cis-trans isomerase A
D: Peptidyl-prolyl cis-trans isomerase A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)77,97012
Polymers74,9934
Non-polymers2,9778
Water13,493749
1
A: GTPase KRas
D: Peptidyl-prolyl cis-trans isomerase A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,9085
Polymers37,4962
Non-polymers1,4123
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: GTPase KRas
C: Peptidyl-prolyl cis-trans isomerase A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,0627
Polymers37,4962
Non-polymers1,5665
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)65.450, 81.460, 127.225
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

-
Protein , 2 types, 4 molecules ABCD

#1: Protein GTPase KRas / K-Ras 2 / Ki-Ras / c-K-ras / c-Ki-ras


Mass: 19372.863 Da / Num. of mol.: 2 / Mutation: G12A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KRAS, KRAS2, RASK2 / Production host: Escherichia coli (E. coli) / References: UniProt: P01116, small monomeric GTPase
#2: Protein Peptidyl-prolyl cis-trans isomerase A / PPIase A / Cyclophilin A / Cyclosporin A-binding protein / Rotamase A


Mass: 18123.582 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PPIA, CYPA / Production host: Escherichia coli (E. coli) / References: UniProt: P62937, peptidylprolyl isomerase

-
Non-polymers , 6 types, 757 molecules

#3: Chemical ChemComp-GNP / PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER


Mass: 522.196 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H17N6O13P3
Comment: GppNHp, GMPPNP, energy-carrying molecule analogue*YM
#4: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#5: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#6: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#7: Chemical ChemComp-ZNI / (1R,5S,6r)-N-[(1P,7S,9S,13S,20M)-20-{5-(4-cyclopropylpiperazin-1-yl)-2-[(1S)-1-methoxyethyl]pyridin-3-yl}-21-ethyl-17,17-dimethyl-8,14-dioxo-15-oxa-4-thia-9,21,27,28-tetraazapentacyclo[17.5.2.1~2,5~.1~9,13~.0~22,26~]octacosa-1(24),2,5(28),19,22,25-hexaen-7-yl]-3-oxabicyclo[3.1.0]hexane-6-carboxamide / RMC-7977


Mass: 865.094 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: C47H60N8O6S / Feature type: SUBJECT OF INVESTIGATION
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 749 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.27 Å3/Da / Density % sol: 45.9 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 8 / Details: 24% PEG4000, 0.1 M Tris-HCl, pH 8.0

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 0.95375 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Jun 16, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.95375 Å / Relative weight: 1
ReflectionResolution: 1.45→63.61 Å / Num. obs: 120928 / % possible obs: 99.94 % / Redundancy: 7.3 % / Biso Wilson estimate: 17.33 Å2 / CC1/2: 0.998 / CC star: 0.999 / Rmerge(I) obs: 0.1037 / Rpim(I) all: 0.04127 / Rrim(I) all: 0.1118 / Net I/σ(I): 8.48
Reflection shellResolution: 1.45→1.502 Å / Redundancy: 7.6 % / Rmerge(I) obs: 1.363 / Mean I/σ(I) obs: 1.18 / Num. unique obs: 11961 / CC1/2: 0.552 / CC star: 0.844 / Rpim(I) all: 0.5292 / Rrim(I) all: 1.463 / % possible all: 99.85

-
Processing

Software
NameVersionClassification
PHENIX1.17.1_3660refinement
PHASERphasing
HKL-2000data reduction
Aimlessdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.45→63.61 Å / SU ML: 0.181 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 21.4977
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2155 5907 4.89 %
Rwork0.1853 114960 -
obs0.1868 120867 99.94 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 24.95 Å2
Refinement stepCycle: LAST / Resolution: 1.45→63.61 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5233 0 200 749 6182
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01585643
X-RAY DIFFRACTIONf_angle_d1.52317649
X-RAY DIFFRACTIONf_chiral_restr0.1186820
X-RAY DIFFRACTIONf_plane_restr0.01984
X-RAY DIFFRACTIONf_dihedral_angle_d14.0762187
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.45-1.470.3141830.31023788X-RAY DIFFRACTION99.87
1.47-1.480.3061840.29753805X-RAY DIFFRACTION99.77
1.48-1.50.29481850.28233798X-RAY DIFFRACTION99.9
1.5-1.520.31921810.26663793X-RAY DIFFRACTION99.92
1.52-1.540.30282130.24843796X-RAY DIFFRACTION99.88
1.54-1.560.26612240.23843740X-RAY DIFFRACTION99.97
1.56-1.580.27121970.2373774X-RAY DIFFRACTION99.87
1.58-1.610.25471940.22053814X-RAY DIFFRACTION99.88
1.61-1.630.24832120.21373792X-RAY DIFFRACTION99.95
1.63-1.660.24491920.21193797X-RAY DIFFRACTION99.92
1.66-1.690.24281670.20383813X-RAY DIFFRACTION99.95
1.69-1.720.25822010.19713813X-RAY DIFFRACTION99.9
1.72-1.750.21041970.19083771X-RAY DIFFRACTION99.95
1.75-1.790.22122160.1913794X-RAY DIFFRACTION99.95
1.79-1.830.21161920.19073824X-RAY DIFFRACTION99.98
1.83-1.870.23081910.19243832X-RAY DIFFRACTION99.93
1.87-1.920.24671770.19013798X-RAY DIFFRACTION99.95
1.92-1.970.22322030.17593830X-RAY DIFFRACTION100
1.97-2.030.21951840.18413834X-RAY DIFFRACTION100
2.03-2.090.2161990.1783826X-RAY DIFFRACTION100
2.09-2.170.22581830.17743841X-RAY DIFFRACTION100
2.17-2.250.21741820.17393863X-RAY DIFFRACTION100
2.25-2.360.21611910.17493826X-RAY DIFFRACTION100
2.36-2.480.19232030.17963855X-RAY DIFFRACTION100
2.48-2.630.22782210.17933837X-RAY DIFFRACTION100
2.63-2.840.20042000.1833877X-RAY DIFFRACTION99.95
2.84-3.120.19152130.18213872X-RAY DIFFRACTION100
3.12-3.580.18682120.16853888X-RAY DIFFRACTION100
3.58-4.50.19832050.16413953X-RAY DIFFRACTION100
4.51-63.610.20572050.17834116X-RAY DIFFRACTION99.79
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)
12.681991838280.157046063602-0.3455331480132.32794047451-0.412860327882.17447419480.1499255602530.03178223006560.306792802230.1540411073060.02244910372970.363491010986-0.324824632928-0.241599403221-0.1435347419310.1544001443770.02622903673540.06024623930250.1413513278860.008546798665640.21521330662-21.1896903633-4.411869474079.98474124354
21.677612795270.367434050024-0.1161820297922.0920244181-0.4889982247773.81377478055-0.04932292804470.1217689821060.0955972553543-0.1469624707080.076503539076-0.136050018478-0.1285018139660.086535803081-0.03007007693650.153522870880.02038858592820.03692118141640.159120967545-0.01834963930430.166517181853-49.059226457917.714282257420.808367572
32.980657390740.5385026669460.5154153507931.8703667438-0.652196059962.252534177850.0692829157699-0.0571184505656-0.155053517150.0239042696679-0.02595881248720.09145291342770.203373018871-0.08793897128-0.03965440190430.1401523949310.02276233155540.01105321379590.102955792313-0.01173741516680.0861490642885-75.749449652125.90267519139.2491077319
42.36511012351-0.3384929659410.4969007382341.166280231960.1170804490762.42228813650.01557256331660.0166163424-0.0917700607326-0.02006602370460.00681403867786-0.02238078645570.2131014731580.0486019289398-0.01637043432810.1129563794358.54170277522E-5-0.00724134150690.05903332254170.008187563279130.0809386996371-24.2159204567-37.900945995310.5503769475
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1(chain 'A' and resid 0 through 169)
2X-RAY DIFFRACTION2(chain 'B' and resid 0 through 169)
3X-RAY DIFFRACTION3(chain 'C' and resid 1 through 165)
4X-RAY DIFFRACTION4(chain 'D' and resid 3 through 165)

+
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