[English] 日本語
Yorodumi
- PDB-9ct8: Tricomplex of Compound 2, KRAS G12D, and CypA -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9ct8
TitleTricomplex of Compound 2, KRAS G12D, and CypA
Components
  • Isoform 2B of GTPase KRas
  • Peptidyl-prolyl cis-trans isomerase A
KeywordsHYDROLASE/HYDROLASE INHIBITOR / KRAS / CypA / G12D / GTPase / tri-complex / inhibitor-complex / HYDROLASE / HYDROLASE-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 / virion binding / leukocyte chemotaxis / 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 / virion binding / leukocyte chemotaxis / negative regulation of stress-activated MAPK cascade / endothelial cell activation / protein peptidyl-prolyl isomerization / forebrain astrocyte development / Basigin interactions / negative regulation of epithelial cell differentiation / cyclosporin A binding / Minus-strand DNA synthesis / Plus-strand DNA synthesis / Uncoating of the HIV Virion / type I pneumocyte differentiation / regulation of synaptic transmission, GABAergic / epithelial tube branching involved in lung morphogenesis / Rac protein signal transduction / Early Phase of HIV Life Cycle / Integration of provirus / 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 / RNA polymerase II CTD heptapeptide repeat P3 isomerase activity / RNA polymerase II CTD heptapeptide repeat P6 isomerase activity / viral release from host cell / skeletal muscle cell differentiation / RAS signaling downstream of NF1 loss-of-function variants / Calcineurin activates NFAT / RUNX3 regulates p14-ARF / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / SHC1 events in ERBB4 signaling / Signalling to RAS / activation of protein kinase B activity / Binding and entry of HIV virion / Activated NTRK2 signals through FRS2 and FRS3 / SHC-related events triggered by IGF1R / Estrogen-stimulated signaling through PRKCZ / glial cell proliferation / positive regulation of viral genome replication / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / 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 oxidative stress-induced intrinsic apoptotic signaling pathway / Erythropoietin activates RAS / Signaling by FGFR4 in disease / SHC-mediated cascade:FGFR1 / FRS-mediated FGFR3 signaling / Signaling by CSF3 (G-CSF) / Signaling by FLT3 ITD and TKD mutants / negative regulation of protein kinase activity / FRS-mediated FGFR2 signaling / protein-membrane adaptor activity / FRS-mediated FGFR4 signaling / p38MAPK events / Signaling by FGFR3 in disease / FRS-mediated FGFR1 signaling / Tie2 Signaling / striated muscle cell differentiation / Signaling by FGFR2 in disease / positive regulation of glial cell proliferation / GRB2 events in EGFR signaling / neutrophil chemotaxis / SHC1 events in EGFR signaling / Signaling by FLT3 fusion proteins / FLT3 Signaling / Signaling by FGFR1 in disease / EGFR Transactivation by Gastrin / homeostasis of number of cells within a tissue / NCAM signaling for neurite out-growth / CD209 (DC-SIGN) signaling / GRB2 events in ERBB2 signaling / Downstream signal transduction / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / Ras activation upon Ca2+ influx through NMDA receptor / SHC1 events in ERBB2 signaling / Insulin receptor signalling cascade / Constitutive Signaling by Overexpressed ERBB2 / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / VEGFR2 mediated cell proliferation / small monomeric GTPase / peptidyl-prolyl cis-trans isomerase activity / positive regulation of protein secretion / peptidylprolyl isomerase / FCERI mediated MAPK activation / RAF activation
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: 1.28 Å
AuthorsZhang, D. / Bar Ziv, T. / Knox, J.E. / Yano, J.K.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Science / Year: 2025
Title: A neomorphic protein interface catalyzes covalent inhibition of RAS
Authors: Wildes, D.
History
DepositionJul 24, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 23, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Isoform 2B of GTPase KRas
B: Isoform 2B of 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)78,08712
Polymers75,0814
Non-polymers3,0068
Water14,178787
1
A: Isoform 2B of GTPase KRas
D: Peptidyl-prolyl cis-trans isomerase A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,0446
Polymers37,5402
Non-polymers1,5034
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Isoform 2B of GTPase KRas
C: Peptidyl-prolyl cis-trans isomerase A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,0446
Polymers37,5402
Non-polymers1,5034
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)47.950, 101.890, 66.060
Angle α, β, γ (deg.)90.000, 91.170, 90.000
Int Tables number4
Space group name H-MP1211
Space group name HallP2yb
Symmetry operation#1: x,y,z
#2: -x,y+1/2,-z

-
Components

-
Protein , 2 types, 4 molecules ABCD

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


Mass: 19416.873 Da / Num. of mol.: 2 / Mutation: G12D
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 , 5 types, 795 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-A1AZX / (2R)-2-amino-N-(2-{[(1R)-1-cyclopentyl-2-{[(1M,8S,10S,14S,21M)-22-ethyl-4-hydroxy-21-{2-[(1R)-1-methoxyethyl]pyridin-3-yl}-18,18-dimethyl-9,15-dioxo-16-oxa-10,22,28-triazapentacyclo[18.5.2.1~2,6~.1~10,14~.0~23,27~]nonacosa-1(25),2(29),3,5,20,23,26-heptaen-8-yl]amino}-2-oxoethyl](methyl)amino}-2-oxoethyl)-N-methylpropanamide (non-preferred name)


Mass: 921.134 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C51H68N8O8
#6: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Cl
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 787 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.15 Å3/Da / Density % sol: 42.76 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop
Details: 22-27% PEG3350 + 0.11-0.20M NaCl + 0.10M MES pH 5.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: PETRA III, EMBL c/o DESY / Beamline: P13 (MX1) / Wavelength: 0.97625 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Sep 8, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97625 Å / Relative weight: 1
ReflectionResolution: 1.28→36.57 Å / Num. obs: 161488 / % possible obs: 99.26 % / Redundancy: 3.8 % / Biso Wilson estimate: 15.51 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.07747 / Net I/σ(I): 7.93
Reflection shellResolution: 1.28→1.326 Å / Rmerge(I) obs: 1.398 / Num. unique obs: 16136 / CC1/2: 0.332

-
Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
HKL-2000data reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.28→31.41 Å / SU ML: 0.156 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 19.8611
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.1903 8062 4.99 %
Rwork0.1502 153410 -
obs0.1522 161472 99.26 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 22.45 Å2
Refinement stepCycle: LAST / Resolution: 1.28→31.41 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5245 0 202 787 6234
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00525707
X-RAY DIFFRACTIONf_angle_d0.88537745
X-RAY DIFFRACTIONf_chiral_restr0.0795825
X-RAY DIFFRACTIONf_plane_restr0.00791007
X-RAY DIFFRACTIONf_dihedral_angle_d12.9122164
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.28-1.290.30142400.27315161X-RAY DIFFRACTION98.97
1.29-1.310.29952700.26775065X-RAY DIFFRACTION98.98
1.31-1.330.31592540.25485136X-RAY DIFFRACTION99.12
1.33-1.340.27892630.25495074X-RAY DIFFRACTION99.11
1.34-1.360.29762770.25365045X-RAY DIFFRACTION99.35
1.36-1.380.31292860.24025083X-RAY DIFFRACTION98.64
1.38-1.40.24922930.21865100X-RAY DIFFRACTION99.72
1.4-1.420.25312590.21585117X-RAY DIFFRACTION99.45
1.42-1.440.26082540.20485135X-RAY DIFFRACTION99.48
1.44-1.470.20173060.1865068X-RAY DIFFRACTION99.5
1.47-1.490.24142630.17325111X-RAY DIFFRACTION99.54
1.49-1.520.21932760.16785115X-RAY DIFFRACTION99.5
1.52-1.550.22642660.16015120X-RAY DIFFRACTION99.52
1.55-1.580.20842510.14825113X-RAY DIFFRACTION99.5
1.58-1.610.19282450.13975167X-RAY DIFFRACTION99.41
1.61-1.650.17952700.13555126X-RAY DIFFRACTION99.21
1.65-1.690.1832570.13245082X-RAY DIFFRACTION99.29
1.69-1.740.18242770.13375076X-RAY DIFFRACTION99.04
1.74-1.790.17852850.13435127X-RAY DIFFRACTION99.12
1.79-1.850.17522560.1445027X-RAY DIFFRACTION97.76
1.85-1.910.20912710.14395130X-RAY DIFFRACTION99.61
1.91-1.990.17122800.13175121X-RAY DIFFRACTION99.7
1.99-2.080.18132570.13535178X-RAY DIFFRACTION99.8
2.08-2.190.17692400.13615122X-RAY DIFFRACTION99.54
2.19-2.330.16932810.13835129X-RAY DIFFRACTION99.69
2.33-2.510.19372760.14865140X-RAY DIFFRACTION99.34
2.51-2.760.19333120.15435090X-RAY DIFFRACTION99.28
2.76-3.160.19812520.14995098X-RAY DIFFRACTION98.69
3.16-3.970.17452600.13065129X-RAY DIFFRACTION98.39
3.97-31.410.15512850.14125225X-RAY DIFFRACTION99.71

+
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