Structure of full length human AMPK in complex with a small molecule activator, a thienopyridone derivative (A-769662)

Structural Basis of Ampk Regulation by Small Molecule Activators.

A 172 THR AND C 172 THR ARE PHOSPHORYLATED.
5'-AMP-ACTIVATED PROTEIN KINASE CATALYTIC SUBUNIT ALPHA-2

B 108 SER AND D 108 SER ARE PHOSPHORYLATED.
5'-AMP-ACTIVATED PROTEIN KINASE SUBUNIT BETA-1

5'-AMP-ACTIVATED PROTEIN KINASE SUBUNIT GAMMA-1

AMPK SUBUNIT ALPHA-2, ACETYL-COA CARBOXYLASE KINASE, ACACA KINASE, HYDROXYMETHYLGLUTARYL-COA REDUCTASE KINASE, HMGCR KINASE

AMPK GAMMA1, AMPK SUBUNIT GAMMA-1, AMPKG

MSHHHHHHSSGLEVLFQGPMAEKQKHDGRVKIGHYVLGDTLGVGTFGKVKIGEHQLTGHKVAVKILNRQKIRSLDVVGKI
KREIQNLKLFRHPHIIKLYQVISTPTDFFMVMEYVSGGELFDYICKHGRVEEMEARRLFQQILSAVDYCHRHMVVHRDLK
PENVLLDAHMNAKIADFGLSNMMSDGEFLR(TPO)SCGSPNYAAPEVISGRLYAGPEVDIWSCGVILYALLCGTLPFDDE
HVPTLFKKIRGGVFYIPEYLNRSVATLLMHMLQVDPLKRATIKDIREHEWFKQDLPSYLFPEDPSYDANVIDDEAVKEVC
EKFECTESEVMNSLYSGDPQDQLAVAYHLIIDNRRIMNQASEFYLASSPPSGSFMDDSAMHIPPGLKPHPERMPPLIADS
PKARCPLDALNTTKPKSLAVKKAKWHLGIRSQSKPYDIMAEVYRAMKQLDFEWKVVNAYHLRVRRKNPVTGNYVKMSLQL
YLVDNRSYLLDFKSIDDEVVEQRSGSSTPQRSCSAAGLHRPRSSFDSTTAESHSLSGSLTGSLTGSTLSSVSPRLGSHTM
DFFEMCASLITTLAR

MSHHHHHHSSGLEVLFQGPMAEKQKHDGRVKIGHYVLGDTLGVGTFGKVKIGEHQLTGHKVAVKILNRQKIRSLDVVGKI
KREIQNLKLFRHPHIIKLYQVISTPTDFFMVMEYVSGGELFDYICKHGRVEEMEARRLFQQILSAVDYCHRHMVVHRDLK
PENVLLDAHMNAKIADFGLSNMMSDGEFLRTSCGSPNYAAPEVISGRLYAGPEVDIWSCGVILYALLCGTLPFDDEHVPT
LFKKIRGGVFYIPEYLNRSVATLLMHMLQVDPLKRATIKDIREHEWFKQDLPSYLFPEDPSYDANVIDDEAVKEVCEKFE
CTESEVMNSLYSGDPQDQLAVAYHLIIDNRRIMNQASEFYLASSPPSGSFMDDSAMHIPPGLKPHPERMPPLIADSPKAR
CPLDALNTTKPKSLAVKKAKWHLGIRSQSKPYDIMAEVYRAMKQLDFEWKVVNAYHLRVRRKNPVTGNYVKMSLQLYLVD
NRSYLLDFKSIDDEVVEQRSGSSTPQRSCSAAGLHRPRSSFDSTTAESHSLSGSLTGSLTGSTLSSVSPRLGSHTMDFFE
MCASLITTLAR

MGLNDIFEAQKIEWHEMGNTSSERAALERHGGHKTPRRDSSGGTKDGDRPKILMDSPEDADLFHSEEIKAPEKEEFLAWQ
HDLEVNDKAPAQARPTVFRWTGGGKEVYLSGSFNNWSKLPLTR(SEP)HNNFVAILDLPEGEHQYKFFVDGQWTHDPSEP
IVTSQLGTVNNIIQVKKTDFEVFDALMVDSQKCSDVSELSSSPPGPYHQEPYVCKPEERFRAPPILPPHLLQVILNKDTG
ISCDPALLPEPNHVMLNHLYALSIKDGVMVLSATHRYKKKYVTTLLYKPI

MGLNDIFEAQKIEWHEMGNTSSERAALERHGGHKTPRRDSSGGTKDGDRPKILMDSPEDADLFHSEEIKAPEKEEFLAWQ
HDLEVNDKAPAQARPTVFRWTGGGKEVYLSGSFNNWSKLPLTRSHNNFVAILDLPEGEHQYKFFVDGQWTHDPSEPIVTS
QLGTVNNIIQVKKTDFEVFDALMVDSQKCSDVSELSSSPPGPYHQEPYVCKPEERFRAPPILPPHLLQVILNKDTGISCD
PALLPEPNHVMLNHLYALSIKDGVMVLSATHRYKKKYVTTLLYKPI

METVISSDSSPAVENEHPQETPESNNSVYTSFMKSHRCYDLIPTSSKLVVFDTSLQVKKAFFALVTNGVRAAPLWDSKKQ
SFVGMLTITDFINILHRYYKSALVQIYELEEHKIETWREVYLQDSFKPLVCISPNASLFDAVSSLIRNKIHRLPVIDPES
GNTLYILTHKRILKFLKLFITEFPKPEFMSKSLEELQIGTYANIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDI
YSKFDVINLAAEKTYNNLDVSVTKALQHRSHYFEGVLKCYLHETLETIINRLVEAEVHRLVVVDENDVVKGIVSLSDILQ
ALVLTGGEKKP

CRYSTALS WERE GROWN BY THE HANGING DROP METHOD WITH RESERVOIR SOLUTION CONTAINING 13% PEG3350, 0.1M MGCL2, 1% GLUCOSE, 0.15% CAPB IN 0.1M IMIDAZOLE AT PH 6.2.

STRUCTURE OF FULL LENGTH HUMAN AMPK IN COMPLEX WITH A SMALL MOLECULE ACTIVATOR, A BENZIMIDAZOLE DERIVATIVE (991)

STRUCTURE OF AN ACTIVE FORM OF MAMMALIAN AMPK

TRANSFERASE, NUCLEOTIDE-BINDING, STAUROSPORINE-BINDING, SERINE/THREONINE-PROTEIN KINASE, ACTIVATOR, CARBOHYDRATE BINDING MODULE (CBM)