Trapping of the Enoyl-Acyl Carrier Protein Reductase-Acyl Carrier Protein Interaction

An ideal target for metabolic engineering, fatty acid biosynthesis remains poorly understood on a molecular level. These carrier protein-dependent pathways require fundamental protein Protein interactions to guide reactivity and processivity, and their control has become one of the major hurdles in...

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Bibliographic Details
Published in:Journal of the American Chemical Society Vol. 138; no. 12; pp. 3962 - 3965
Main Authors: Tallorin, Lorillee, Finzel, Kara, Nguyen, Quynh G., Beld, Joris, La Clair, James J., Burkart, Michael D.
Format: Journal Article
Language:English
Published: WASHINGTON Amer Chemical Soc 30.03.2016
Subjects:
Acyl Carrier Protein - metabolism
Chemistry
Chemistry, Multidisciplinary
Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) - isolation & purification
Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) - metabolism
Escherichia coli - enzymology
Escherichia coli Proteins - isolation & purification
Escherichia coli Proteins - metabolism
Fatty Acid Synthase, Type II - isolation & purification
Fatty Acid Synthase, Type II - metabolism
Models, Molecular
Molecular Structure
Oxidoreductases - isolation & purification
Oxidoreductases - metabolism
Physical Sciences
Protein Binding
Protein Engineering
Science & Technology
Triclosan - chemistry
Triclosan - metabolism
TARGET
TRICLOSAN
FABI
INHIBITION
FATTY-ACID BIOSYNTHESIS
MECHANISM
ANALOGS
PLASMODIUM-FALCIPARUM
ESCHERICHIA-COLI
BINDING
ISSN:0002-7863, 1520-5126
Online Access:Get more information
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Summary:An ideal target for metabolic engineering, fatty acid biosynthesis remains poorly understood on a molecular level. These carrier protein-dependent pathways require fundamental protein Protein interactions to guide reactivity and processivity, and their control has become one of the major hurdles in successfully adapting these biological machines. Our laboratory has developed methods to prepare acyl carrier proteins (ACPs) loaded with substrate mimetics and cross-linkers to visualize and trap interactions with partner enzymes, and we continue to expand the tools for studying these pathways. We now describe application of the slow-onset, tight-binding inhibitor triclosan to explore the interactions between the type II fatty acid ACP from Escherichia coli, AcpP,, and its corresponding enoyl-ACP Teductase, FabI. We show that the AcpP-triclosan complex demonstrates nM binding, inhibits in vitro activity, and can be used to isolate FabI in complex proteomes.
Bibliography:NIH RePORTER
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ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.5b13456