1PYN

DUAL-SITE POTENT, SELECTIVE PROTEIN TYROSINE PHOSPHATASE 1B INHIBITOR USING A LINKED FRAGMENT STRATEGY AND A MALONATE HEAD ON THE FIRST SITE

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	7.1	277	PRECIPITATION BUFFER: 100 mM HEPES, 0.2 M Magnesisum Acetate, 14% PEG8000, pH 7.10, VAPOR DIFFUSION, HANGING DROP, temperature 277K

Crystal Properties
Matthews coefficient	Solvent content
3.18	61.38

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 88.71	α = 90
b = 88.71	β = 90
c = 104.83	γ = 120

Symmetry
Space Group	P 31 2 1

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray	100	CCD	MARRESEARCH	MIRRORS	2001-05-09	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	ROTATING ANODE	RIGAKU RU300

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Merge I (Observed)	R Sym I (Observed)	Net I Over Average Sigma (I)	Redundancy	Number Reflections (All)	Number Reflections (Observed)	Observed Criterion Sigma (F)	Observed Criterion Sigma (I)	B (Isotropic) From Wilson Plot
1	2.1	20	94	0.057	0.057	20.2	4.5	26734	25276		1	29.4

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	R-Sym I (Observed)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
	2.1	2.18	73		0.338	0.338	2.23	2.5	2784

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Starting model	Resolution (High)	Resolution (Low)	Cut-off Sigma (F)	Number Reflections (All)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Factor (All)	R-Factor (Observed)	R-Work	R-Free	R-Free Selection Details	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	THROUGHOUT	PDB ENTRY 1TYR AND INITIAL INTERNAL REFINEMENT OF OTHER COMPLEXES. RESIDUE CYS215, LISTED IN REMARK 500, CORRESPONDS TO THE ACTIVE SITE CYS WHICH IS KNOWN TO BE IN A STRAINED CONFORMATION IN THIS CLASS OF ENZYMES.	2.2	19.74	2	25245	22184	2219	78.3	0.212	0.211	0.198	0.224	RANDOM	32.1

Temperature Factor Modeling
Anisotropic B[1][1]	Anisotropic B[1][2]	Anisotropic B[1][3]	Anisotropic B[2][2]	Anisotropic B[2][3]	Anisotropic B[3][3]
2.45	2.98		2.45		-4.89

RMS Deviations
Key	Refinement Restraint Deviation
c_dihedral_angle_d	22.4
c_scangle_it	5.06
c_scbond_it	3.71
c_mcangle_it	3.34
c_mcbond_it	2.27
c_angle_deg	1.3
c_improper_angle_d	0.72
c_bond_d	0.007

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2301
Nucleic Acid Atoms
Solvent Atoms	251
Heterogen Atoms	43

Software

Software
Software Name	Purpose
MAR345	data collection
HKL-2000	data reduction
CNX	refinement
HKL-2000	data scaling
CNX	phasing

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.