Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A

Dual specificity tyrosine-phosphorylation-regulated kinase 1A

Protein kinase minibrain homolog, MNBH, hMNB, HP86, Dual specificity YAK1-related kinase

GASDSSHKKERKVYNDGYDDDNYDYIVKNGEKWMDRYEIDSLIGKGSFGQVVKAYDRVEQEWVAIKIIKNKKAFLNQAQI
EVRLLELMNKHDTEMKYYIVHLKRHFMFRNHLCLVFEMLSYNLYDLLRNTNFRGVSLNLTRKFAQQMCTALLFLATPELS
IIHCDLKPENILLCNPKRSAIKIVDFGSSCQLGQRIYQ(PTR)IQSRFYRSPEVLLGMPYDLAIDMWSLGCILVEMHTGE
PLFSGANEVDQMNKIVEVLGIPPAHILDQAPKARKFFEKLPDGTWNLKKTKDGKREYKPPGTRKLHNILGVETGGPGGRR
AGESGHTVADYLKFKDLILRMLDYDPKTRIQPYYALQHSFFKKTADEGTNTS

GASDSSHKKERKVYNDGYDDDNYDYIVKNGEKWMDRYEIDSLIGKGSFGQVVKAYDRVEQEWVAIKIIKNKKAFLNQAQI
EVRLLELMNKHDTEMKYYIVHLKRHFMFRNHLCLVFEMLSYNLYDLLRNTNFRGVSLNLTRKFAQQMCTALLFLATPELS
IIHCDLKPENILLCNPKRSAIKIVDFGSSCQLGQRIYQYIQSRFYRSPEVLLGMPYDLAIDMWSLGCILVEMHTGEPLFS
GANEVDQMNKIVEVLGIPPAHILDQAPKARKFFEKLPDGTWNLKKTKDGKREYKPPGTRKLHNILGVETGGPGGRRAGES
GHTVADYLKFKDLILRMLDYDPKTRIQPYYALQHSFFKKTADEGTNTS

0.1M sodium cacodylate, 0.2M sodium acetate, 30% PEG 4000, pH 6.5, VAPOR DIFFUSION, HANGING DROP, temperature 293K

BULK SOLVENT MODEL USED; Non-crystallographic-symmetry restrain used

protein kinase, TRANSFERASE, TRANSFERASE-TRANSFERASE INHIBITOR complex

DSSHKKERKVYNDGYDDDNYDYIVKNGEKWMDRYEIDSLIGKGSFGQVVKAYDRVEQEWVAIKIIKNKKAFLNQAQIEVR
LLELMNKHDTEMKYYIVHLKRHFMFRNHLCLVFEMLSYNLYDLLRNTNFRGVSLNLTRKFAQQMCTALLFLATPELSIIH
CDLKPENILLCNPKRSAIKIVDFGSSCQLGQRIYQYIQSRFYRSPEVLLGMPYDLAIDMWSLGCILVEMHTGEPLFSGAN
EVDQMNKIVEVLGIPPAHILDQAPKARKFFEKLPDGTWNLKKTKDGKREYKPPGTRKLHNILGVETGGPGGRRAGESGHT
VADYLKFKDLILRMLDYDPKTRIQPYYALQHSFFKKTADEGTNTS