Non-homologous isofunctional enzymes

A non-homologous isofunctional enzyme (NISE) is analogous in function to a known enzyme, but share unique protein sequence or folding (Omelchenko et al., 2010). As such, there may be confusion regarding the Enzyme Commission number system.

A recent example is of the enzyme urate hydroxylase (EC 1.14.13.113) which catalyzes the decomposition of urate, an important constituent of nitrogen cycling. The newly discovered HpyO gene was non-homologous in sequence to the original gene HpxO (O'leary et al., 2009) but yet shared certain characteristics enabling it to perform a similar reaction (Michiel et al., 2012).

References

• Marina V Omelchenko, Michael Y Galperin, Yuri I Wolf and Eugene V Koonin. (2010). Non-homologous isofunctional enzymes: A systematic analysis of alternative solutions in enzyme evolution. Biology Direct, 5(31).
• Seán E. O’Leary, Katherine A. Hicks, Steven E. Ealick, and Tadhg P. Begley. (2009). Biochemical Characterization of the HpxO Enzyme from Klebsiella pneumoniae, a Novel FAD–Dependent Urate Oxidase. Biochemistry. 2009 April 14; 48(14): 3033–3035. doi:10.1021/bi900160b.
• Magalie Michiel, Nadia Perchat, Alain Perret, Sabine Tricot, Aude Papeil, Marielle Besnard, Véronique de Berardinis, Marcel Salanoubat, and Cécile Fischer. (2012). Microbial urate catabolism: characterization of HpyO, a non-homologous isofunctional isoform of the flavoprotein urate hydroxylase HpxO. Environmental Microbiology reports 4 (6): 642–647. doi:10.1111/j.1758-2229.2012.00390.x. PMID 23760935