5CXA

Crystal structure of the catalytic domain of Human MMP12 in complex with a carboxylate inhibitor related to RXP470

X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
Type	Source	Accession Code	Details
experimental model	PDB	4GQL

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP	10	293	Protein: hMMP12 F171D K241A at 608 micro-M + 10 milli-M AHA + 0.552 milli-M inhibitor. precipitant: 26% PEG4000, 3% dioxane, 0.114 M TRIS pH 10. cryoprotectant: 10 % diethylene glycol + 5 % glycerol + 10 % 2,3-butanediol + 5 % 1,4-dioxane, 25% PEG 6K, 0.1 M TRIS-HCl, pH 8.0

Crystal Properties
Matthews coefficient	Solvent content
2.29	46.18

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 69.23	α = 90
b = 63.7	β = 90
c = 36.62	γ = 90

Symmetry
Space Group	P 21 21 2

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray	100	PIXEL	DECTRIS PILATUS 6M	bent cylindrical mirror	2014-09-07	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	ESRF BEAMLINE ID23-2	0.8729	ESRF	ID23-2

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	1.3	46.88	99.9	0.165	0.155	9.23	9.05	40627	40584		-3

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	1.3	1.38	99.3		1.39	1.24	8.67

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Starting model	Resolution (High)	Resolution (Low)	Cut-off Sigma (F)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Factor (Observed)	R-Work	R-Free	R-Free Selection Details	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	THROUGHOUT	4GQL	1.3	36.62	1.35	40581	2030	99.89	0.1423	0.1403	0.181	RANDOM

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]

RMS Deviations
Key	Refinement Restraint Deviation
f_dihedral_angle_d	26.262
f_angle_d	0.848
f_chiral_restr	0.076
f_bond_d	0.005
f_plane_restr	0.005

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	1242
Nucleic Acid Atoms
Solvent Atoms	285
Heterogen Atoms	50

Software

Software
Software Name	Purpose
PHENIX	refinement
Coot	model building
XDS	data reduction
MxCuBE	data collection
XDS	data scaling
MOLREP	phasing

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), 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 R01GM157729.