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- PDB-10nu: Structure of kRas G12C bound to Inhibitor 13ab -

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Basic information

Entry
Database: PDB / ID: 10nu
TitleStructure of kRas G12C bound to Inhibitor 13ab
ComponentsGTPase KRas
KeywordsONCOPROTEIN / KRAS / SMALL GTPASE / INHIBITOR Complex
Function / homology
Function and homology information


negative regulation of epithelial cell differentiation / response to mineralocorticoid / GMP binding / forebrain astrocyte development / epithelial tube branching involved in lung morphogenesis / LRR domain binding / regulation of synaptic transmission, GABAergic / response to isolation stress / type I pneumocyte differentiation / skeletal muscle cell differentiation ...negative regulation of epithelial cell differentiation / response to mineralocorticoid / GMP binding / forebrain astrocyte development / epithelial tube branching involved in lung morphogenesis / LRR domain binding / regulation of synaptic transmission, GABAergic / response to isolation stress / type I pneumocyte differentiation / skeletal muscle cell differentiation / response to gravity / myoblast proliferation / Rac protein signal transduction / cardiac muscle cell proliferation / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants / Activation of RAS in B cells / positive regulation of glial cell proliferation / RAS signaling downstream of NF1 loss-of-function variants / homeostasis of number of cells within a tissue / RUNX3 regulates p14-ARF / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / SHC1 events in ERBB4 signaling / glial cell proliferation / Signalling to RAS / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / Estrogen-stimulated signaling through PRKCZ / positive regulation of Rac protein signal transduction / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / SHC-mediated cascade:FGFR2 / SHC-mediated cascade:FGFR4 / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / Erythropoietin activates RAS / SHC-mediated cascade:FGFR1 / Signaling by FGFR4 in disease / striated muscle cell differentiation / 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 / Signaling by FGFR3 in disease / FRS-mediated FGFR1 signaling / Tie2 Signaling / protein-membrane adaptor activity / Signaling by FGFR2 in disease / Signaling by FLT3 fusion proteins / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / FLT3 Signaling / Signaling by FGFR1 in disease / EGFR Transactivation by Gastrin / NCAM signaling for neurite out-growth / CD209 (DC-SIGN) signaling / liver development / Downstream signal transduction / GRB2 events in ERBB2 signaling / response to glucocorticoid / Insulin receptor signalling cascade / SHC1 events in ERBB2 signaling / Constitutive Signaling by Overexpressed ERBB2 / Ras activation upon Ca2+ influx through NMDA receptor / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / VEGFR2 mediated cell proliferation / small monomeric GTPase / FCERI mediated MAPK activation / regulation of long-term neuronal synaptic plasticity / female pregnancy / Signaling by ERBB2 TMD/JMD mutants / visual learning / Signaling by SCF-KIT / Constitutive Signaling by EGFRvIII / RAF activation / Signaling by high-kinase activity BRAF mutants / Signaling by ERBB2 ECD mutants / MAP2K and MAPK activation / Signaling by ERBB2 KD Mutants / neuron apoptotic process / gene expression / cytokine-mediated signaling pathway / cytoplasmic side of plasma membrane / Signaling by RAF1 mutants / Signaling by CSF1 (M-CSF) in myeloid cells / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / MAPK cascade / Negative regulation of MAPK pathway / RAS processing / Regulation of RAS by GAPs / positive regulation of cellular senescence / Signaling by BRAF and RAF1 fusions / GDP binding
Similarity search - Function
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
: / GUANOSINE-5'-DIPHOSPHATE / GTPase KRas
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.5 Å
AuthorsShaffer, P.L. / Milligan, C. / Peters, U.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2026
Title: Optimization of Covalent 6-Cyanoquinazoline KRAS G12C Inhibitors for the Treatment of Solid Tumors.
Authors: Waldo, J.P. / Krawczuk, P.J. / Kelly, C.B. / Callas, C.G. / Cisar, J.S. / Eccles, W. / Guerrero, C.A. / Hack, M.D. / Jones, W.M. / Keohane, C.E. / Li, L.S. / Meegalla, S. / Padilla-Salinas, ...Authors: Waldo, J.P. / Krawczuk, P.J. / Kelly, C.B. / Callas, C.G. / Cisar, J.S. / Eccles, W. / Guerrero, C.A. / Hack, M.D. / Jones, W.M. / Keohane, C.E. / Li, L.S. / Meegalla, S. / Padilla-Salinas, R. / Rosano, R.J. / Shimkin, K.W. / Simonnet, Y.R.F. / Sitkoff, D. / Sookezian, A. / Winters, M.P. / Bush, T.L. / Cheung, S.T. / Del Rosario, A.M. / Hansen, R. / Janes, M.R. / Janjua, H. / Kazmi, F. / Kirkpatrick, R. / La, D. / Lenhart, R. / Lorenzi, M.V. / Liu, Y. / Mesens, N. / Milligan, C.M. / Murrey, H. / Peters, U. / Ren, P. / Richter, M. / Rizzolio, M. / Rao, S. / Shaffer, P. / Stratton, C.F. / Szewczuk, L.M. / Wen, J. / Wong, V. / Yanovich, C. / Laquerre, S. / Edwards, J.P. / Leonard, K.A.
History
DepositionJan 29, 2026Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 15, 2026Provider: repository / Type: Initial release
Revision 1.1Apr 29, 2026Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: GTPase KRas
B: GTPase KRas
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,15312
Polymers38,7062
Non-polymers2,44710
Water4,864270
1
A: GTPase KRas
hetero molecules


Theoretical massNumber of molelcules
Total (without water)20,5766
Polymers19,3531
Non-polymers1,2245
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: GTPase KRas
hetero molecules


Theoretical massNumber of molelcules
Total (without water)20,5766
Polymers19,3531
Non-polymers1,2245
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)33.554, 40.042, 61.773
Angle α, β, γ (deg.)77.10, 81.70, 77.60
Int Tables number1
Space group name H-MP1

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Components

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Protein , 1 types, 2 molecules AB

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


Mass: 19352.785 Da / Num. of mol.: 2 / Mutation: G12C; C51S; C80L; C118S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KRAS, KRAS2, RASK2 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P01116

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Non-polymers , 5 types, 280 molecules

#2: Chemical
ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Formula: Ca
#3: Chemical ChemComp-A1C6Y / 1-((2R,5S)-4-((S)-6-chloro-7-(1,6-dimethyl-1H-indazol-7-yl)-8-fluoro-2-(((S)-1-methylpyrrolidin-2-yl)methoxy)quinazolin-4-yl)-2,5-dimethylpiperazin-1-yl)prop-2-en-1-one / 1-{(2R,5S)-4-[(7M)-6-chloro-7-(1,6-dimethyl-1H-indazol-7-yl)-8-fluoro-2-{[(2S)-1-methylpyrrolidin-2-yl]methoxy}quinazolin-4-yl]-2,5-dimethylpiperazin-1-yl}propan-1-one


Mass: 608.149 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C32H39ClFN7O2 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical ChemComp-GDP / GUANOSINE-5'-DIPHOSPHATE


Type: RNA linking / Mass: 443.201 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H15N5O11P2 / Comment: GDP, energy-carrying molecule*YM
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 270 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

CrystalDensity Matthews: 2.03 Å3/Da / Density % sol: 39.44 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.5 / Details: 25-29% PEG4000, 0.2 M CaCl2, 0.1 M Tris pH 8.5

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 5, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.5→59.9 Å / Num. obs: 37264 / % possible obs: 89.3 % / Redundancy: 3.5 % / CC1/2: 0.994 / Rmerge(I) obs: 0.087 / Rpim(I) all: 0.053 / Net I/σ(I): 5.3
Reflection shellResolution: 1.5→1.58 Å / Redundancy: 3.2 % / Rmerge(I) obs: 0.417 / Mean I/σ(I) obs: 1.9 / Num. unique obs: 1850 / CC1/2: 0.835 / Rpim(I) all: 0.397 / % possible all: 53.6

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Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
STARANISO2.4.9data scaling
XDS20220820data reduction
PDB_EXTRACTdata extraction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.5→35.66 Å / SU ML: 0.19 / Cross valid method: FREE R-VALUE / σ(F): 1.97 / Phase error: 33.44 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2694 1898 5.1 %
Rwork0.2429 --
obs0.2443 37250 76.16 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.5→35.66 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2636 0 158 270 3064
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0052946
X-RAY DIFFRACTIONf_angle_d1.0554034
X-RAY DIFFRACTIONf_dihedral_angle_d16.615465
X-RAY DIFFRACTIONf_chiral_restr0.076451
X-RAY DIFFRACTIONf_plane_restr0.007506
LS refinement shellResolution: 1.5→1.55 Å
RfactorNum. reflection% reflection
Rfree0.352 57 -
Rwork0.305 950 -
obs--18.88 %
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)
10.2924-0.05250.03440.40420.02490.4999-0.06260.11580.11880.00410.00490.0154-0.01280.008-0.16150.03450.0222-0.00410.13880.09620.100253.5819-3.75848.7594
20.5545-0.1137-0.15290.3770.09780.4805-0.0842-0.0564-0.0071-0.02470.0455-0.0131-0.00260.0365-0.00270.0484-0.01710.01430.0152-0.03790.037171.61888.9026-19.4241
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1(chain A and resseq 2:205 )
2X-RAY DIFFRACTION2(chain B and resseq 1:205)

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