Identification and characterization of new family members in the tautomerase superfamily: Analysis and implications

• Published in: Archives of biochemistry and biophysics 2014-12, Vol.564, p.189-196
• Main Authors: Huddleston, Jamison P., Burks, Elizabeth A., Whitman, Christian P.
• Format: Article
• Language: English
• Subjects: 4-Oxalocrotonate tautomerase; Bacteria - enzymology; Bacteria - genetics; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Carboxy-Lyases - chemistry; Carboxy-Lyases - genetics; Carboxy-Lyases - metabolism; Catalytic amino terminal proline; Catalytic promiscuity; Hydratase activity; Isomerases - chemistry; Isomerases - genetics; Isomerases - metabolism; Malonate semialdehyde decarboxylase; Structural Homology, Protein; Tautomerase superfamily; β–α–β fold
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2014.08.019

[Display omitted] •4-OT homologues are found in biosynthetic and catabolic pathways.•The MSAD hydratase activity might be a biological activity for an unknown substrate.•The tautomerase superfamily is rich in metabolic diversity. Tautomerase superfamily members are characterized by a β–α–β building block and a catalytic amino terminal proline. 4-Oxalocrotonate tautomerase (4-OT) and malonate semialdehyde decarboxylase (MSAD) are the title enzymes of two of the five known families in the superfamily. Two recent developments in these families indicate that there might be more metabolic diversity in the tautomerase superfamily than previously thought. 4-OT homologues have been identified in three biosynthetic pathways, whereas all previously characterized 4-OTs are found in catabolic pathways. In the MSAD family, homologues have been characterized that lack decarboxylase activity, but have a modest hydratase activity using 2-oxo-3-pentynoate. This observation stands in contrast to the first characterized MSAD, which is a proficient decarboxylase and a less efficient hydratase. The hydratase activity was thought to be a vestigial and promiscuous activity. However, this recent discovery suggests that the hydratase activity might reflect a new activity in the MSAD family for an unknown substrate. These discoveries open up new avenues of research in the tautomerase superfamily.