4AN2

Crystal structures of human MEK1 with carboxamide-based allosteric inhibitor XL518 (GDC-0973), or related analogs.

Experimental procedure

Experimental method	SINGLE WAVELENGTH
Source type	SYNCHROTRON
Source details	ALS BEAMLINE 8.2.1
Synchrotron site	ALS
Beamline	8.2.1
Temperature [K]	100
Detector technology	CCD
Collection date	2005-11-15
Detector	ADSC QUANTUM 315r
Spacegroup name	P 61
Unit cell lengths	108.844, 108.844, 47.710
Unit cell angles	90.00, 90.00, 120.00

Refinement procedure

Resolution	94.070 - 2.500
R-factor	0.21493
Rwork	0.211
R-free	0.29898
Structure solution method	MOLECULAR REPLACEMENT
Starting model (for MR)	IN HOUSE MEK1-AMPPCP STRUCTURE
RMSD bond length	0.021
RMSD bond angle	2.178
Data reduction software	MOSFLM
Data scaling software	SCALA
Phasing software	MOLREP
Refinement software	REFMAC (5.2.0005)

Data quality characteristics

	Overall	Outer shell
Low resolution limit [Å]	54.390	2.680
High resolution limit [Å]	2.500	2.500
Rmerge	0.070	0.560
Number of reflections	12819
<I/σ(I)>	15.2	2.3
Completeness [%]	99.8	99.9
Redundancy	4.4	4.2

Crystallization Conditions

crystal ID	method	pH	temperature	details
1		8.9		MEK1 (8 MG/ML) WAS INCUBATED WITH INHIBITOR (300 MICROMOLAR FINAL CONCENTRATION) AND AMPPCP (2.8 MM FINAL CONCENTRATION) FOR TWO HOURS ON ICE, FOLLOWED BY CRYSTALLIZION VS. 26.5% PEG-2000 MME, 0.1 M TRIMETHYLAMINE N- OXIDE AND 0.1 M TRIS (PH 8.9)