Nguyen H

References (2)

Title : Trypanosoma brucei Acyl-Protein Thioesterase-like (TbAPT-L) Is a Lipase with Esterase Activity for Short and Medium-Chain Fatty Acids but Has No Depalmitoylation Activity - Brown_2022_Pathogens_11_1245
Author(s) : Brown RWB , Sharma AI , Villanueva MR , Li X , Onguka O , Zilbermintz L , Nguyen H , Falk BA , Olson CL , Taylor JM , Epting CL , Kathayat RS , Amara N , Dickinson BC , Bogyo M , Engman DM
Ref : Pathogens , 11 : , 2022
Abstract : Dynamic post-translational modifications allow the rapid, specific, and tunable regulation of protein functions in eukaryotic cells. S-acylation is the only reversible lipid modification of proteins, in which a fatty acid, usually palmitate, is covalently attached to a cysteine residue of a protein by a zDHHC palmitoyl acyltransferase enzyme. Depalmitoylation is required for acylation homeostasis and is catalyzed by an enzyme from the alpha/beta hydrolase family of proteins usually acyl-protein thioesterase (APT1). The enzyme responsible for depalmitoylation in Trypanosoma brucei parasites is currently unknown. We demonstrate depalmitoylation activity in live bloodstream and procyclic form trypanosomes sensitive to dose-dependent inhibition with the depalmitoylation inhibitor, palmostatin B. We identified a homologue of human APT1 in Trypanosoma brucei which we named TbAPT-like (TbAPT-L). Epitope-tagging of TbAPT-L at N- and C- termini indicated a cytoplasmic localization. Knockdown or over-expression of TbAPT-L in bloodstream forms led to robust changes in TbAPT-L mRNA and protein expression but had no effect on parasite growth in vitro, or cellular depalmitoylation activity. Esterase activity in cell lysates was also unchanged when TbAPT-L was modulated. Unexpectedly, recombinant TbAPT-L possesses esterase activity with specificity for short- and medium-chain fatty acid substrates, leading to the conclusion, TbAPT-L is a lipase, not a depalmitoylase.
ESTHER : Brown_2022_Pathogens_11_1245
PubMedSearch : Brown_2022_Pathogens_11_1245
PubMedID: 36364996
Gene_locus related to this paper: tryb2-q7yxi0

Title : Thioesterase enzyme families: Functions, structures, and mechanisms - Caswell_2021_Protein.Sci__
Author(s) : Caswell BT , de Carvalho CC , Nguyen H , Roy M , Nguyen T , Cantu DC
Ref : Protein Science , : , 2021
Abstract : Thioesterases are enzymes that hydrolyze thioester bonds in numerous biochemical pathways, for example in fatty acid synthesis. This work reports known functions, structures, and mechanisms of updated thioesterase enzyme families, which are classified into 35 families based on sequence similarity. Each thioesterase family is based on at least one experimentally characterized enzyme, and most families have enzymes that have been crystallized and their tertiary structure resolved. Classifying thioesterases into families allows to predict tertiary structures and infer catalytic residues and mechanisms of all sequences in a family, which is particularly useful because the majority of known protein sequence have no experimental characterization. Phylogenetic analysis of experimentally characterized thioesterases that have structures with the two main structural folds reveal convergent and divergent evolution. Based on tertiary structure superimposition, catalytic residues are predicted.
ESTHER : Caswell_2021_Protein.Sci__
PubMedSearch : Caswell_2021_Protein.Sci__
PubMedID: 34921469