Crystal Structure of the PDE4D Catalytic Domain and UCR2 Regulatory Helix with T-48

Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders.

cAMP-specific 3',5'-cyclic phosphodiesterase 4D

MSIPRFGVKTEQEDVLAKELEDVNKWGLHVFRIAELSGNRPLTVIMHTIFQERDLLKTFKIPVDTLITYLMTLEDHYHAD
VAYHNNIHAADVVQSTHVLLSTPALEAVFTDLEILAAIFASAIHDVDHPGVSNQFLINTNSELALMYNDSSVLENHHLAV
GFKLLQEENCDIFQNLTKKQRQSLRKMVIDIVLATDMSKHMNLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLQNMVHC
ADLSNPTKPLQLYRQWTDRIMEEFFRQGDRERERGMEISPMCDKHNASVEKSQVGFIDYIVHPLWETWADLVHPDAQDIL
DTLEDNREWYQSTIPQAPAPPLDEQNRDSQGNQVSEFISNTFLDENLYFQ

4.6MG/ML VCID7620 + 0.5MM T-048-1
1MM DTT, 0.1MM ZNCL2, 0.1MM MGCL2 (BATCH 1214013) AGAINST
SPARSE MATRIX CONDITION MORPHEUS C4, 12.5% W/V PEG1,000 ,
12.5% W/V PEG3,350 , 12.5% W/V MPD , 0.03M NPS (SODIUM
NITRATE, DISODIUM HYDROGEN PHOSPHATE, AMMONIUM SULFATE), 0.1M
MES/IMIDAZOLE PH 6.5, CRYO-PROTECTED - DIRECT (QYM9-2), VAPOR
DIFFUSION, SITTING DROP, TEMPERATURE 289K

National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)

PDE4D, CAMP-SPECIFIC 3'5'-CYCLIC PHOSPHODIESTERASE 4D, UCR2, cAMP, HYDROLASE, HYDROLASE-HYDROLASE INHIBITOR complex

SIPRFGVKTEQEDVLAKELEDVNKWGLHVFRIAELSGNRPLTVIMHTIFQERDLLKTFKIPVDTLITYLMTLEDHYHADV
AYHNNIHAADVVQSTHVLLSTPALEAVFTDLEILAAIFASAIHDVDHPGVSNQFLINTNSELALMYNDSSVLENHHLAVG
FKLLQEENCDIFQNLTKKQRQSLRKMVIDIVLATDMSKHMNLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLQNMVHCA
DLSNPTKPLQLYRQWTDRIMEEFFRQGDRERERGMEISPMCDKHNASVEKSQVGFIDYIVHPLWETWADLVHPDAQDILD
TLEDNREWYQSTIPQSPSP