Structural highlights
Publication Abstract from PubMed
The parasitic protozoa, Leishmania major, produces a peroxidase (abbreviated LmP) that exhibits activities characteristic of both yeast cytochrome c peroxidase (CCP) and plant cytosolic ascorbate peroxidase (APX). One common feature is a key Trp residue, Trp208 in LmP and Trp191 in CCP, that is situated adjacent to the proximal His heme ligand in CCP, APX and LmP. In CCP Trp191 forms a stable cationic radical after reaction with H2O2 to form Compound I; in APX the radical is located on the porphyrin ring. In order to clarify the role of Trp208 in LmP and to further probe peroxidase structure-function relationships we have determined the crystal structure of LmP and have studied the role of Trp208 using electron paramagnetic resonance spectroscopy (EPR), mutagenesis, and enzyme kinetics. Both CCP and LmP have an extended section of beta structure near Trp191 and 208, respectively, which is absent in APX. This region provides stability to the Trp191 radical in CCP. EPR of LmP Compound I exhibits an intense and stable signal similar to CCP Compound I. In the LmP Trp208Phe mutant this signal disappears indicating that Trp208 forms a stable cationic radical. In LmP conversion of the Cys197 to Thr significantly weakens the Compound I EPR signal and dramatically lowers enzyme activity. These results further support the view that modulation of the local electrostatic environment controls the stability of the Trp radical in peroxidases. Our results also suggest that the biological role of LmP is to function as a cytochrome c peroxdase.
The crystal structure of Leishmania major peroxidase and characterization of the compound I tryptophan radical.,Jasion VS, Polanco JA, Meharenna YT, Li H, Poulos TL J Biol Chem. 2011 May 13. PMID:21566139[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jasion VS, Polanco JA, Meharenna YT, Li H, Poulos TL. The crystal structure of Leishmania major peroxidase and characterization of the compound I tryptophan radical. J Biol Chem. 2011 May 13. PMID:21566139 doi:10.1074/jbc.M111.230524
