NIH VideoCast - NIH Director's Seminar Series: How the fat gets on proteins – structure and mechanism of enzymes that catalyze protein palmitoylation

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NIH Director's Seminar Series: How the fat gets on proteins – structure and mechanism of enzymes that catalyze protein palmitoylation

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Air date:	Friday, May 19, 2023, 12:00:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 128 (78 Live, 50 On-demand)
Category:	NIH Director's Seminars
Runtime:	00:56:07
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	Posttranslational modification of proteins by attachment of lipids touches almost all areas of cellular physiology. One of the major areas of interest in our lab are integral membrane enzymes that catalyze protein lipidation. The most widely prevalent form of protein lipidation is protein S-acylation or protein palmitoylation whereby membrane proximal cysteines are modified by fatty acids through a thioester linkage. Protein palmitoylation, owing to its inherent lability through the action of cellular thioesterases, offers a unique, potentially dynamic form of protein lipidation. There are 23 members of the DHHC family of integral membrane enzymes that catalyze protein palmitoylation and several thousand cellular proteins that are known to be palmitoylated. Yet, nothing was known till recently about their three-dimensional structure or detailed mechanism of action. Our work has led to the first high-resolution structure of two DHHC palmitoyltransferases and detailed insights into their chemical mechanism. They have enabled us to design engineered versions of human DHHC20 that open up the possibility of designing new tools for probing the physiology of DHHC enzymes. Chemical and pharmacological small molecule probes for DHHC enzymes are sorely lacking and our structural studies are also plausible starting points for such a small molecule probe discovery program.

NLM Title:	How the fat gets on proteins : structure and mechanism of enzymes that catalyze protein palmitoylation / Anirban Banerjee.
Author:	Banerjee, Anirban. National Institutes of Health (U.S.),
Publisher:
Abstract:	(CIT): Posttranslational modification of proteins by attachment of lipids touches almost all areas of cellular physiology. One of the major areas of interest in our lab are integral membrane enzymes that catalyze protein lipidation. The most widely prevalent form of protein lipidation is protein S-acylation or protein palmitoylation whereby membrane proximal cysteines are modified by fatty acids through a thioester linkage. Protein palmitoylation, owing to its inherent lability through the action of cellular thioesterases, offers a unique, potentially dynamic form of protein lipidation. There are 23 members of the DHHC family of integral membrane enzymes that catalyze protein palmitoylation and several thousand cellular proteins that are known to be palmitoylated. Yet, nothing was known till recently about their three-dimensional structure or detailed mechanism of action. Our work has led to the first high-resolution structure of two DHHC palmitoyltransferases and detailed insights into their chemical mechanism. They have enabled us to design engineered versions of human DHHC20 that open up the possibility of designing new tools for probing the physiology of DHHC enzymes. Chemical and pharmacological small molecule probes for DHHC enzymes are sorely lacking and our structural studies are also plausible starting points for such a small molecule probe discovery program.
Subjects:	Lipolysis--physiology Lipoylation--physiology Protein Processing, Post-Translational--genetics Proteolysis
Publication Types:	Lecture Webcast
NLM Classification:	QU 85.6
NLM ID:	9918625743006676
CIT Live ID:	49743
Permanent link:	https://videocast.nih.gov/watch=49743

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