Dataset Information

Functional Annotation of ABHD14B, an Orphan Serine Hydrolase Enzyme.

ABSTRACT: The metabolic serine hydrolase family is, arguably, one of the largest functional enzyme classes in mammals, including humans, comprising 1-2% of the total proteome. This enzyme family uses a conserved nucleophilic serine residue in the active site to perform diverse hydrolytic reactions and consists of proteases, lipases, esterases, amidases, and transacylases, which are prototypical members of this family. In humans, this enzyme family consists of >250, of which approximately 40% members remain unannotated, in terms of both their endogenous substrates and the biological pathways that they regulate. The enzyme ABHD14B, an outlying member of this family, is also known as CCG1/TAFII250-interacting factor B, as it was found to be associated with transcription initiation factor TFIID. The crystal structure of human ABHD14B was determined more than a decade ago; however, its endogenous substrates remain elusive. In this paper, we annotate ABHD14B as a lysine deacetylase (KDAC), showing this enzyme's ability to transfer an acetyl group from a post-translationally acetylated lysine to coenzyme A (CoA), to yield acetyl-CoA, while regenerating the free amine of protein lysine residues. We validate these findings by in vitro biochemical assays using recombinantly purified human ABHD14B in conjunction with cellular studies in a mammalian cell line by knocking down ABHD14B and by identification of a putative substrate binding site. Finally, we report the development and characterization of a much-needed, exquisitely selective ABHD14B antibody, and using it, we map the cellular and tissue distribution of ABHD14B and prospective metabolic pathways that this enzyme might biologically regulate.

SUBMITTER: Rajendran A

PROVIDER: S-EPMC6976303 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Functional Annotation of ABHD14B, an Orphan Serine Hydrolase Enzyme.

Rajendran Abinaya A Vaidya Kaveri K Mendoza Johnny J Bridwell-Rabb Jennifer J Kamat Siddhesh S SS

Biochemistry 20190913 2

The metabolic serine hydrolase family is, arguably, one of the largest functional enzyme classes in mammals, including humans, comprising 1-2% of the total proteome. This enzyme family uses a conserved nucleophilic serine residue in the active site to perform diverse hydrolytic reactions and consists of proteases, lipases, esterases, amidases, and transacylases, which are prototypical members of this family. In humans, this enzyme family consists of >250, of which approximately 40% members remai ...[more]

PMID: 31478652

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Dataset Information

Functional Annotation of ABHD14B, an Orphan Serine Hydrolase Enzyme.

Publications

Functional Annotation of ABHD14B, an Orphan Serine Hydrolase Enzyme.

Similar Datasets

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