Crystal structure of PDE10A2 with fragment ZT214

Identification and Optimization of PDE10A Inhibitors Using Fragment-Based Screening by Nanocalorimetry and X-ray Crystallography.

cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A

GAGTSICTSEEWQGLMQFTLPVRLCKEIELFHFDIGPFENMWPGIFVYMVHRSCGTSCFELEKLCRFIMSVKKNYRRVPY
HNWKHAVTVAHCMYAILQNNHTLFTDLERKGLLIACLCHDLDHRGFSNSYLQKFDHPLAALYSTSTMEQHHFSQTVSILQ
LEGHNIFSTLSSSEYEQVLEIIRKAIIATDLALYFGNRKQLEEMYQTGSLNLNNQSHRDRVIGLMMTACDLCSVTKLWPV
TKLTANDIYAEFWAEGDEMKKLGIQPIPMMDRDKKDEVPQGQLGFYNAVAIPCYTTLTQILPPTEPLLKACRDNLSQWEK
VIRGEETATWISSPSVAQKAAASED

18% PEG 4450, 0.2M calcium acetate, 50mM BME, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 277K

THE FOUR DIVALENT CATIONS ARE REPRESENTED BY NI BUT THIS IDENTIFICATION IS SPECULATIVE

fragment screening, hydrolase, HYDROLASE-HYDROLASE INHIBITOR complex

SICTSEEWQGLMQFTLPVRLCKEIELFHFDIGPFENMWPGIFVYMVHRSCGTSCFELEKLCRFIMSVKKNYRRVPYHNWK
HAVTVAHCMYAILQNNHTLFTDLERKGLLIACLCHDLDHRGFSNSYLQKFDHPLAALYSTSTMEQHHFSQTVSILQLEGH
NIFSTLSSSEYEQVLEIIRKAIIATDLALYFGNRKQLEEMYQTGSLNLNNQSHRDRVIGLMMTACDLCSVTKLWPVTKLT
ANDIYAEFWAEGDEMKKLGIQPIPMMDRDKKDEVPQGQLGFYNAVAIPCYTTLTQILPPTEPLLKACRDNLSQWEKVIRG
EETATWISSPSVAQKAAASED