Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding. / Langendorf, Christopher G.; Ngoei, Kevin R.W.; Scott, John W.; Ling, Naomi X.Y.; Issa, Sam M.A.; Gorman, Michael A.; Parker, Michael W.; Sakamoto, Kei; Oakhill, Jonathan S.; Kemp, Bruce E.

In: Nature Communications, Vol. 7, 10912, 08.03.2016.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Langendorf, CG, Ngoei, KRW, Scott, JW, Ling, NXY, Issa, SMA, Gorman, MA, Parker, MW, Sakamoto, K, Oakhill, JS & Kemp, BE 2016, 'Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding', Nature Communications, vol. 7, 10912. https://doi.org/10.1038/ncomms10912

APA

Langendorf, C. G., Ngoei, K. R. W., Scott, J. W., Ling, N. X. Y., Issa, S. M. A., Gorman, M. A., Parker, M. W., Sakamoto, K., Oakhill, J. S., & Kemp, B. E. (2016). Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding. Nature Communications, 7, [10912]. https://doi.org/10.1038/ncomms10912

Vancouver

Langendorf CG, Ngoei KRW, Scott JW, Ling NXY, Issa SMA, Gorman MA et al. Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding. Nature Communications. 2016 Mar 8;7. 10912. https://doi.org/10.1038/ncomms10912

Author

Langendorf, Christopher G. ; Ngoei, Kevin R.W. ; Scott, John W. ; Ling, Naomi X.Y. ; Issa, Sam M.A. ; Gorman, Michael A. ; Parker, Michael W. ; Sakamoto, Kei ; Oakhill, Jonathan S. ; Kemp, Bruce E. / Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding. In: Nature Communications. 2016 ; Vol. 7.

Bibtex

@article{9402df3e51b0485b84efe011b6656223,
title = "Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding",
abstract = "The metabolic stress-sensing enzyme AMP-activated protein kinase (AMPK) is responsible for regulating metabolism in response to energy supply and demand. Drugs that activate AMPK may be useful in the treatment of metabolic diseases including type 2 diabetes. We have determined the crystal structure of AMPK in complex with its activator 5-(5-hydroxyl-isoxazol-3-yl)-furan-2-phosphonic acid (C2), revealing two C2-binding sites in the γ-subunit distinct from nucleotide sites. C2 acts synergistically with the drug A769662 to activate AMPK α1-containing complexes independent of upstream kinases. Our results show that dual drug therapies could be effective AMPK-targeting strategies to treat metabolic diseases.",
author = "Langendorf, {Christopher G.} and Ngoei, {Kevin R.W.} and Scott, {John W.} and Ling, {Naomi X.Y.} and Issa, {Sam M.A.} and Gorman, {Michael A.} and Parker, {Michael W.} and Kei Sakamoto and Oakhill, {Jonathan S.} and Kemp, {Bruce E.}",
year = "2016",
month = mar,
day = "8",
doi = "10.1038/ncomms10912",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding

AU - Langendorf, Christopher G.

AU - Ngoei, Kevin R.W.

AU - Scott, John W.

AU - Ling, Naomi X.Y.

AU - Issa, Sam M.A.

AU - Gorman, Michael A.

AU - Parker, Michael W.

AU - Sakamoto, Kei

AU - Oakhill, Jonathan S.

AU - Kemp, Bruce E.

PY - 2016/3/8

Y1 - 2016/3/8

N2 - The metabolic stress-sensing enzyme AMP-activated protein kinase (AMPK) is responsible for regulating metabolism in response to energy supply and demand. Drugs that activate AMPK may be useful in the treatment of metabolic diseases including type 2 diabetes. We have determined the crystal structure of AMPK in complex with its activator 5-(5-hydroxyl-isoxazol-3-yl)-furan-2-phosphonic acid (C2), revealing two C2-binding sites in the γ-subunit distinct from nucleotide sites. C2 acts synergistically with the drug A769662 to activate AMPK α1-containing complexes independent of upstream kinases. Our results show that dual drug therapies could be effective AMPK-targeting strategies to treat metabolic diseases.

AB - The metabolic stress-sensing enzyme AMP-activated protein kinase (AMPK) is responsible for regulating metabolism in response to energy supply and demand. Drugs that activate AMPK may be useful in the treatment of metabolic diseases including type 2 diabetes. We have determined the crystal structure of AMPK in complex with its activator 5-(5-hydroxyl-isoxazol-3-yl)-furan-2-phosphonic acid (C2), revealing two C2-binding sites in the γ-subunit distinct from nucleotide sites. C2 acts synergistically with the drug A769662 to activate AMPK α1-containing complexes independent of upstream kinases. Our results show that dual drug therapies could be effective AMPK-targeting strategies to treat metabolic diseases.

UR - http://www.scopus.com/inward/record.url?scp=84960416125&partnerID=8YFLogxK

U2 - 10.1038/ncomms10912

DO - 10.1038/ncomms10912

M3 - Journal article

C2 - 26952388

AN - SCOPUS:84960416125

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 10912

ER -

ID: 239212507