Architectural Organization of the Metabolic Regulatory Enzyme Ghrelin O-Acyltransferase

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Characterization of Ghrelin O-acyltransferase Active Site

Ghrelin, first discovered in 1999, is a 28-amino acid peptide hormone involved in the regulation of appetite, insulin secretion and sensitivity, and many neurological effects such as learning, memory, and depression.1-6 Ghrelin has been identified to have a unique posttranslational octanoylation carried out by the enzyme ghrelin O-acyltransferase (GOAT). This distinctive modification is a point...

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The discovery of ghrelin O-acyltransferase (GOAT) opens the way to the design of drugs that block the attachment of an octanoyl group to the appetite-stimulating peptide hormone ghrelin, potentially preventing obesity. Here, we develop a biochemical assay that uses membranes from insect cells infected with baculovirus encoding mouse GOAT. The GOAT-containing membranes transferred the [(3)H]octa...

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Characterization of Ghrelin O-Acyltransferase (GOAT) in goldfish (Carassius auratus)

Ghrelin is the only known hormone posttranslationally modified with an acylation. This modification is crucial for most of ghrelin's physiological effects and is catalyzed by the polytopic enzyme ghrelin O-acyltransferase (GOAT). The aim of this study was to characterize GOAT in a teleost model, goldfish (Carassius auratus). First, the full-length cDNA sequence was obtained by RT-PCR and rapid ...

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A small molecule antagonist of ghrelin O-acyltransferase (GOAT).

Using our recently disclosed fluorescence-based assay to monitor acyltransferase activity, the first non-peptidic, small molecule antagonists of ghrelin O-acyltransferase (GOAT), a potential anti-obesity and anti-diabetes target, have been discovered. Each exhibits micromolar inhibition of the enzyme, and may be useful probes for future study of the ghrelin-GOAT system.

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Colocalization of ghrelin O-acyltransferase and ghrelin in gastric mucosal cells.

Ghrelin is a peptide hormone with many known functions, including orexigenic, blood glucose-regulatory, and antidepressant actions, among others. Mature ghrelin is unique in that it is the only known naturally occurring peptide to be posttranslationally modified by O-acylation with octanoate. This acylation is required for many of ghrelin's actions, including its effects on promoting increases ...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2013

ISSN: 0021-9258

DOI: 10.1074/jbc.m113.510313