PROSITE documentation PDOC00065

3-hydroxyacyl-CoA dehydrogenase signature

3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35) (HCDH) [1] is an enzyme involved in fatty acid metabolism, it catalyzes the reduction of 3-hydroxyacyl-CoA to 3-oxoacyl-CoA. Most eukaryotic cells have 2 fatty-acid β-oxidation systems, one located in mitochondria and the other in peroxisomes. In peroxisomes 3-hydroxyacyl-CoA dehydrogenase forms, with enoyl-CoA hydratase (ECH) and 3,2-trans-enoyl-CoA isomerase (ECI) a multifunctional enzyme where the N-terminal domain bears the hydratase/isomerase activities and the C-terminal domain the dehydrogenase activity. There are two mitochondrial enzymes: one which is monofunctional and the other which is, like its peroxisomal counterpart, multifunctional.

In Escherichia coli (gene fadB) and Pseudomonas fragi (gene faoA) HCDH is part of a multifunctional enzyme which also contains an ECH/ECI domain as well as a 3-hydroxybutyryl-CoA epimerase domain [2].

The other proteins structurally related to HCDH are:

• Bacterial 3-hydroxybutyryl-CoA dehydrogenase (EC 1.1.1.157) which reduces 3-hydroxybutanoyl-CoA to acetoacetyl-CoA [3].
• Eye lens protein lambda-crystallin [4], which is specific to lagomorphes (such as rabbit).

There are two major region of similarities in the sequences of proteins of the HCDH family, the first one located in the N-terminal, corresponds to the NAD-binding site, the second one is located in the center of the sequence. We have chosen to derive a signature pattern from this central region.