6XIH

Structure-guided optimization of a novel class of ASK1 inhibitors with increased sp3 character and an exquisite selectivity profile

Experimental procedure

Experimental method	SINGLE WAVELENGTH
Source type	SYNCHROTRON
Source details	ALS BEAMLINE 5.0.3
Synchrotron site	ALS
Beamline	5.0.3
Temperature [K]	100
Detector technology	CCD
Collection date	2014-08-22
Detector	ADSC QUANTUM 315r
Wavelength(s)	0.9760
Spacegroup name	P 65 2 2
Unit cell lengths	78.910, 78.910, 429.705
Unit cell angles	90.00, 90.00, 120.00

Refinement procedure

Resolution	30.000 - 2.650
R-factor	0.2275
Rwork	0.221
R-free	0.29170
Structure solution method	MOLECULAR REPLACEMENT
Starting model (for MR)	5usq
RMSD bond length	0.007
RMSD bond angle	1.568
Data reduction software	HKL-2000
Data scaling software	HKL-2000
Phasing software	PHASER
Refinement software	REFMAC (5.8.0257)

Data quality characteristics

	Overall	Inner shell	Outer shell
Low resolution limit [Å]	50.000	50.000	2.680
High resolution limit [Å]	2.630	7.130	2.630
Rmerge	0.109	0.032
Rmeas	0.115	0.034
Rpim	0.041	0.011	0.604
Total number of observations	261550
Number of reflections	24937	1476	1167
<I/σ(I)>	6.4
Completeness [%]	99.9	98.7	99.7
Redundancy	10.5	9.2	10.3
CC(1/2)		0.999	0.668

Crystallization Conditions

crystal ID	method	pH	temperature	details
1	VAPOR DIFFUSION, SITTING DROP	6	277	6% polyethylene glycol 2000 MME , 20% glycerol, 0.1M MES, pH 6.0