5KYK

Covalent GTP-competitive inhibitors of KRAS G12C: Guanosine bisphosphonate Analogs

Experimental procedure

Experimental method	SINGLE WAVELENGTH
Source type	SYNCHROTRON
Source details	APS BEAMLINE 19-ID
Synchrotron site	APS
Beamline	19-ID
Temperature [K]	100
Detector technology	CCD
Collection date	2015-06-19
Detector	ADSC QUANTUM 315
Wavelength(s)	0.979
Spacegroup name	C 1 2 1
Unit cell lengths	114.830, 66.155, 98.006
Unit cell angles	90.00, 112.98, 90.00

Refinement procedure

Resolution	43.741 - 2.702
R-factor	0.2695
Rwork	0.267
R-free	0.31440
Structure solution method	MOLECULAR REPLACEMENT
Starting model (for MR)	4nmm
RMSD bond length	0.002
RMSD bond angle	0.478
Data reduction software	HKL-2000
Data scaling software	HKL-2000
Phasing software	PHENIX
Refinement software	PHENIX (1.10.1_2155)

Data quality characteristics

	Overall	Inner shell	Outer shell
Low resolution limit [Å]	50.000	50.000	2.700
High resolution limit [Å]	2.650	7.190	2.650
Rmerge	0.073	0.039
Rmeas	0.078	0.043
Rpim	0.033	0.017	0.696
Total number of observations	126113
Number of reflections	19876
<I/σ(I)>	9.3
Completeness [%]	99.8	99	98.1
Redundancy	6.3	6.2	4.6
CC(1/2)		0.998	0.459

Crystallization Conditions

crystal ID	method	pH	temperature	details
1	EVAPORATION		293	Protein was purified in buffer: 20 mM Hepes pH 8.0, 150 mM NaCl, 5 mM MgCl2 and 0.5 mM DTT. Crystals grew in five days at room temperature from hanging vapor diffusion drops with following condition: 0.1 M Citric acid pH 4.0, 20% PEG 3350. Crystals were cryoprotected in mother liquid with 40% PEG 3350 and flash frozen in liquid nitrogen.