Dissertation/Thesis Abstract

Structural and biochemical characterization of the Saccharomyces cerevisiae AMPK homolog SNF1
by Amodeo, Gabriele A., Ph.D., Columbia University, 2009, 246; 3373706
Abstract (Summary)

The 5' AMP-activated protein kinase (AMPK) is a master regulator of energy homeostasis. AMPK is activated by a high AMP:ATP ratio, and functions as a metabolic thermostat. By sensing when energy is low, AMPK can upregulate energy-producing pathways while also downregulating energy-consuming pathways. It helps regulate such pathways as glycolysis, gluconeogenesis, glucose transport, and fatty acid synthesis and oxidation. In addition, AMPK plays a part in controlling food intake. Due to its central role in regulating these processes, AMPK represents a key drug target for both diabetes and obesity. The importance of AMPK is further underscored by its conservation among all eukaryotic organisms; in S. cerevisiae, the AMPK homolog is named SNF1. SNF1 controls many of the same pathways as AMPK.

This thesis describes the structural and functional characterization of SNF1. The structures of the catalytic protein kinase domain, regulatory Bateman2 domain, and heterotrimer core of SNF1 are presented herein. Our studies elucidate important differences between SNF1 and higher eukaryotic AMPKs, especially with regards to AMP activation. In addition, we have provided the first structural insight into several regions of SNF1 important for regulation of protein kinase activity. Finally, we used biochemical experiments to characterize the interface between two regulatory regions of SNF1.

Indexing (document details)
Advisor: Tong, Liang
School: Columbia University
School Location: United States -- New York
Source: DAI-B 70/08, Dissertation Abstracts International
Subjects: Molecular biology
Keywords: AMPK, Catalytic protein kinase domains, Energy regulation, Heterotrimer core, SNF1, Structural biology
Publication Number: 3373706
ISBN: 978-1-109-34490-5
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