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PANTHER Family Information   
Family: THIOESTERASE (PTHR11487)
Subfamilies: 1
PANTHER Links:
Tree  Multiple Sequence Alignment
Tree  MSA
Abstract:

This family contains thioesterases involved in non-ribosomal peptide biosynthesis or polyketide biosynthesis, as well as those involved in vertebrate fatty acid biosynthesis (medium-chain S-acyl fatty acid synthase thioesterases, EC: 3.1.2.14). Based on domain architecture, they belong to type II (stand-alone, non-integrated) thioesterases (TEII). Based on the structural fold, they belong to the thioesterases of the alpha/beta hydrolase fold. This group of thioesterases is distantly related to the integrated (type I) thioeterases that are intrinsic components of animal fatty acid synthase (PIRSF: PIRSF000453) and in this context serve to terminate chain elongation.

This family contains thioesterases involved in non-ribosomal peptide biosynthesis or polyketide biosynthesis, as well as those involved in vertebrate fatty acid biosynthesis (medium-chain S-acyl fatty acid synthase thioesterases, EC: 3.1.2.14). Based on domain architecture, they belong to type II (stand-alone, non-integrated) thioesterases (TEII). Based on the structural fold, they belong to the thioesterases of the alpha/beta hydrolase fold. This group of thioesterases is distantly related to the integrated (type I) thioeterases that are intrinsic components of animal fatty acid synthase (PIRSF: PIRSF000453) and in this context serve to terminate chain elongation.

Prokaryotic members of this family are involved in non-ribosomal peptide biosynthesis or polyketide biosynthesis. Type I polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) are organised into modules, each adding one fatty acid or amino acid substrate to a growing chain [PMID:10508662]. Synthetic intermediates are covalently tethered by thioester linkages to a carrier protein domain in each module. Cyclization and release of the product is catalysed by the type I thioesterase (TEI) which is usually fused C-terminally to the last module (integrated) [PMID:11001063, PMID:10508662, PMID:12416979, PMID:12005429, PMID:11401555]. In most systems, another component, type II thioesterase, represented by this family, is also present. For example, SrfTE is a TEI domain embedded at the downstream end of the final subunit, SrfC [PMID:12005429], and SrfA-TE is a stand-alone TEII [PMID:9560421]. These enzymes are not essential; however, they are important for effective synthesis, because deletion of the genes leads to a drastic reduction in product yields [PMID:9560421]. TEII enzymes that are associated with the synthetases of the peptide antibiotics surfactin (TEIIsrf) and bacitracin (TEIIbac) were shown to efficiently regenerate miss-acylated thiol groups of 4 -phosphopantetheine (4 PP) cofactors attached to the peptidyl carrier proteins (PCPs) of NRPSs [PMID:12384573]. Therefore, the role of TEIIs in non-ribosomal peptide synthesis is the regeneration of miss-acylated NRPSs, which result from the apo to holo conversion of NRPS enzymes because of the promiscuity of dedicated 4 PP transferases that use not only free CoA, but also acyl-CoAs as 4 PP donors [PMID:12384573].

Members of this family from vertebrates are medium-chain S-acyl fatty acid synthase thioesterases (TEII, EC: 3.1.2.14). They are tissue-specific (found in mammary glands of nonruminants and uropygial glands of waterfowl) chain-terminating enzymes of the fatty acid biosynthesis pathway for the synthesis of shorter chain fatty acids instead of palmitic acid as the major product. TEIIs are stand-alone enzymes that interact with the fatty acid synthase complex and catalyse premature release of the growing acyl chain [PMID:2318831, PMID:3968077].

Thioesterases are classified into two structural classes: those with a classical alpha/beta hydrolase fold, containing a classic Ser-His-Asp triad in the active site [PMID:11080636] (e.g., this family, PIRSF: PIRSF019701), and those with a "hot dog" fold [PMID:8805534] (e.g., INTERPRO: IPR003703, PIRSF: PIRSF003230, PIRSF: PIRSF016607, etc). Typically, those of the former class act on acylated proteins (Acyl-ACP etc), while those of the latter class act on CoA thioesters. Members of this family, as well as related integrated non-ribosomal peptide/polyketide biosynthesis thioesterases (e.g., PIRSF: PIRSF001610) and FAS thioesterases (PIRSF: PIRSF000453), belong to the alpha/beta hydrolase fold class [PMID:12005429].

Nomenclature note: In the Escherichia coli nomenclature, there are thioesterase I (TesA, PIRSF: PIRSF019701) and thioesterae II (TesB, INTERPRO: IPR003703) enzymes. This nomenclature is not derived from the type I and type II classification based on domain architecture (note that both TesA and TesB are stand-alone thioesterases). Therefore, the term TEII is being used by different authors either as a reference to the stand-alone type TE or as a reference to the TesB group, or both.


InterPro Accession: IPR012223
PANTHER Molecular Function: Hydrolase
   Other hydrolase

PANTHER Biological Process: Other metabolism

Pathway Categories: No pathway information available
Training Sequences: 15
HMM Length 299
Downloads: HMM (HMMER format)

Genes assigned to this Family
  Total Celera NCBI
H. sapiens 2 1 1
M. musculus 2 1 1
R. norvegicus 2 1 1
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