Determinants of oligosaccharide specificity of the carbohydrate-binding modules of AMP-activated protein kinase

The Biochemical Journal
Jesse I MobbsPaul R Gooley

Abstract

AMP-activated protein kinase (AMPK) is an αβγ heterotrimer that is important in regulating energy metabolism in all eukaryotes. The β-subunit exists in two isoforms (β1 and β2) and contains a carbohydrate-binding module (CBM) that interacts with glycogen. The two CBM isoforms (β1- and β2-CBM) are near identical in sequence and structure, yet show differences in carbohydrate-binding affinity. β2-CBM binds linear carbohydrates with 4-fold greater affinity than β1-CBM and binds single α1,6-branched carbohydrates up to 30-fold tighter. To understand these affinity differences, especially for branched carbohydrates, we determined the NMR solution structure of β2-CBM in complex with the single α1,6-branched carbohydrate glucosyl-β-cyclodextrin (gBCD) which supported the dynamic nature of the binding site, but resonance broadening prevented defining where the α1,6 branch bound. We therefore solved the X-ray crystal structures of β1- and β2-CBM, in complex with gBCD, to 1.7 and 2.0 Å (1 Å=0.1 nm) respectively. The additional threonine (Thr101) of β2-CBM expands the size of the surrounding loop, creating a pocket that accommodates the α1,6 branch. Hydrogen bonds are formed between the α1,6 branch and the backbone of Trp99 and Lys102 sid...Continue Reading

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Citations

Feb 24, 2016·Acta Pharmaceutica Sinica. B·David Grahame Hardie
Dec 9, 2015·Trends in Plant Science·Shane EmanuellePaul R Gooley
Oct 30, 2015·Journal of Medicinal Chemistry·Marie MiglianicoDietbert Neumann
May 6, 2016·Cellular and Molecular Life Sciences : CMLS·Shane EmanuelleMatthew S Gentry
Dec 2, 2017·Chembiochem : a European Journal of Chemical Biology·Jesse I MobbsPaul R Gooley
Apr 14, 2018·Acta Crystallographica. Section D, Structural Biology·Jingxu GuoMuhummad Akhtar
Apr 22, 2016·American Journal of Physiology. Cell Physiology·Hongyang XuRobyn M Murphy
Mar 5, 2016·The FEBS Journal·Fiona A RossD Grahame Hardie
Aug 28, 2020·Frontiers in Cellular and Infection Microbiology·Diana M Dunn, Joshua Munger
Oct 31, 2018·International Journal of Molecular Sciences·Natalie R JanzenNolan J Hoffman
Sep 20, 2019·Biotechnology Advances·Štefan JanečekBirte Svensson

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