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Title: Crystal Structure of the Protein Kinase Domain of Yeast AMP-Activated Protein Kinase Snf1

Abstract

AMP-activated protein kinase (AMPK) is a master metabolic regulator, and is an important target for drug development against diabetes, obesity, and other diseases. AMPK is a hetero-trimeric enzyme, with a catalytic ({alpha}) subunit, and two regulatory ({beta} and {gamma}) subunits. Here we report the crystal structure at 2.2 Angstrom resolution of the protein kinase domain (KD) of the catalytic subunit of yeast AMPK (commonly known as SNF1). The Snf1-KD structure shares strong similarity to other protein kinases, with a small N-terminal lobe and a large C-terminal lobe. Two negative surface patches in the structure may be important for the recognition of the substrates of this kinase.

Authors:
; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
913706
Report Number(s):
BNL-78274-2007-JA
Journal ID: ISSN 0006-291X; BBRCA9; TRN: US200804%%161
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochem. Biophys. Res. Commun.; Journal Volume: 337
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; CRYSTAL STRUCTURE; DISEASES; METABOLIC DISEASES; PHOSPHOTRANSFERASES; PROTEINS; RESOLUTION; SUBSTRATES; TARGETS; YEASTS; national synchrotron light source

Citation Formats

Rudolph,M., Amodeo, G., Bai, Y., and Tong, L.. Crystal Structure of the Protein Kinase Domain of Yeast AMP-Activated Protein Kinase Snf1. United States: N. p., 2005. Web. doi:10.1016/j.bbrc.2005.09.181.
Rudolph,M., Amodeo, G., Bai, Y., & Tong, L.. Crystal Structure of the Protein Kinase Domain of Yeast AMP-Activated Protein Kinase Snf1. United States. doi:10.1016/j.bbrc.2005.09.181.
Rudolph,M., Amodeo, G., Bai, Y., and Tong, L.. Sat . "Crystal Structure of the Protein Kinase Domain of Yeast AMP-Activated Protein Kinase Snf1". United States. doi:10.1016/j.bbrc.2005.09.181.
@article{osti_913706,
title = {Crystal Structure of the Protein Kinase Domain of Yeast AMP-Activated Protein Kinase Snf1},
author = {Rudolph,M. and Amodeo, G. and Bai, Y. and Tong, L.},
abstractNote = {AMP-activated protein kinase (AMPK) is a master metabolic regulator, and is an important target for drug development against diabetes, obesity, and other diseases. AMPK is a hetero-trimeric enzyme, with a catalytic ({alpha}) subunit, and two regulatory ({beta} and {gamma}) subunits. Here we report the crystal structure at 2.2 Angstrom resolution of the protein kinase domain (KD) of the catalytic subunit of yeast AMPK (commonly known as SNF1). The Snf1-KD structure shares strong similarity to other protein kinases, with a small N-terminal lobe and a large C-terminal lobe. Two negative surface patches in the structure may be important for the recognition of the substrates of this kinase.},
doi = {10.1016/j.bbrc.2005.09.181},
journal = {Biochem. Biophys. Res. Commun.},
number = ,
volume = 337,
place = {United States},
year = {Sat Jan 01 00:00:00 EST 2005},
month = {Sat Jan 01 00:00:00 EST 2005}
}
  • The 5'-AMP (adenosine monophosphate)-activated protein kinase (AMPK) coordinates metabolic function with energy availability by responding to changes in intracellular adenosine triphosphate (ATP) and AMP levels. Here we report crystal structures at 2.6 and 2.9 Angstrom resolution for ATP- and AMP-bound forms of a core {alpha}{beta}{gamma} adenylate-binding domain from the fission yeast AMPK homologue. ATP and AMP bind competitively to a single site in the {gamma} subunit, with their respective phosphate groups positioned near function-impairing mutants. Surprisingly, ATP binds without counter ions, amplifying its electrostatic effects on a critical regulatory region where all three subunits converge.
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