Fig. 6: VcHdaH belongs to sub-cluster 5b and is a de-decanoylase.
From: Distribution and diversity of classical deacylases in bacteria
a AlphaFold2 structure prediction of BsAcuC (2c) shows a typical arginase-deacetylase fold with a central eight-stranded parallel β-sheet surrounded by α-helices. Right panel: The crystal structure of the enzyme VcHdaH (5b) reveals the binding of a decanoic acid in the foot pocket. The foot pocket is arranged almost perpendicular to the substrate binding tunnel leading to the active site. The structure shows coordination of the active site Zn2+-ion by the decanoic acid carboxylate in a bidentate fashion. The electrostatics were plotted onto the interior surface of the VcHdaH (5b) structure using the APBS plugin in PyMOL220. This shows an extended foot pocket to accommodate the decanoic acid. This pocket is negatively charged. b Structural superposition of the structure of VcHdaH (5b) and human HDAC11 (5f) suggest similar molecular mechanisms underlying the observed activities as de-fatty acylases. As no experimental structure is known for human HDAC11, an AlphaFold2 model was used here. For both, an extended foot pocket is present allowing to release the products of the deacylation reaction. Both enzymes are capable of acting as deacylases for longer acyl-chains. The structural superposition shows the structural similarity of the foot pockets in human HDAC11 (5f) and VcHdaH (5b).
