HotDog domain


In molecular biology, the HotDog domain is a protein structural motif found in a diverse superfamily of enzymes, primarily thioesterases and dehydratases. The name "HotDog" refers to its characteristic structure, where a central α-helix is wrapped by a curved β-sheet.

Structure

The HotDog domain consists of a central α-helix and an antiparallel β-sheet that wraps around the α-helix. The basic structural unit of HotDog domain proteins is typically a homodimer, formed by the association of two monomers or two tandem copies of the domain. However, more complex quaternary structures, including tetramers and hexamers, have been observed.

Function

Proteins containing the HotDog domain are primarily involved in thioester hydrolysis, various ehydration reactions and acyl transfer reactions. Hotdog fold protein play roles in various metabolic pathways, such as fatty acid biosynthesis and degradation, polyketide biosynthesis and phenylacetic acid degradation.

Enzyme families

The HotDog domain superfamily includes several enzyme families, such as:

Catalytic mechanism

The catalytic mechanism of HotDog domain enzymes varies depending on the specific enzyme and reaction. However, many of these enzymes share common features in their active sites including a conserved catalytic triad or dyad, often including aspartate, glutamate, or serine residues. A nucleophilic attack mechanism, typically involving an activated water molecule and substrate binding sites that accommodate the CoA moiety and the acyl group.

Evolution and distribution

HotDog domain proteins are found in all three domains of life: Bacteria, Archaea, and Eukaryota. Their widespread distribution suggests an ancient evolutionary origin. Despite low overall sequence similarity, the structural conservation of the HotDog fold implies a common ancestor for these diverse enzymes.