XplA is a P450-flavodoxin fusion enzyme that mediates the metabolism of the military explosive RDX (1,3,5-trinitro-1,3,5-triazinane) in Rhodococcus rhodochrous 11Y [1]. Bui et al. have conducted a detailed spectroscopic and crystallographic study of this unusual hemoflavoprotein [2, 3].
The XplA P450 has evolved as a reductase (rather than oxidase) of RDX and structural alterations to its heme- and FMN-binding domains have led to reduction potentials for low-spin heme iron Fe3+/Fe2+ and FMNSQ/HQ couples being much more positive than those seen in typical P450s and flavodoxins, but consistent with non-oxidative P450 catalysis. These evolutionary steps have also led to a constricted P450 active site with high affinity for RDX (but also for the small heterocyclic inhibitor imidazole), and also to substantially diminished affinity for FMN in the flavodoxin domain.
- Rylott, E.L., Jackson, R.G., Sabbadin, F., Seth-Smith, H.M.B., Edwards, J., Chong, C.S., Strand, S.E., Grogan, G. and Bruce, N.C. (2011) The explosive-degrading cytochrome P450 XplA: biochemistry, structural features and prospects for bioremediation. Biochim. Biophys. Acta 1814, 230—236.
- Bui, S.H., McLean, K.J., Cheesman, M.R., Bradley, J.M., Rigby, S.E.J., Levy, C.W., Leys, D. and Munro, A.W. (2012) Unusual spectroscopic and ligand binding properties of the cytochrome P450-flavodoxin fusion enzyme XplA. J. Biol. Chem. 287, 19699—19714.
- PDB:4EP6
