Amyloid β chaperone - lipocalin-type prostaglandin D synthase acts as a peroxidase in the presence of heme.

Amyloid β chaperone - lipocalin-type prostaglandin D synthase acts as a peroxidase in the presence of heme. Biochem J. 2020 Apr 17;477(7):1227-1240 Authors: Phillips M, Kannaian B, Yang JNT, Kather R, Yuguang M, Harmer JR, Pervushin K Abstract The extracellular transporter, lipocalin-type prostaglandin D synthase (L-PGDS) binds to heme and heme metabolites with high affinity. It has been reported that L-PGDS protects neuronal cells against apoptosis induced by exposure to hydrogen peroxide. Our study demonstrates that when human WT L-PGDS is in complex with heme, it exhibits a strong peroxidase activity thus behaving as a pseudo-peroxidase. Electron paramagnetic resonance studies confirm that heme in the L-PGDS-heme complex is hexacoordinated with high-spin Fe(III). NMR titration of heme in L-PGDS points to hydrophobic interaction between heme and several residues within the β-barrel cavity of L-PGDS. In addition to the transporter function, L-PGDS is a key amyloid β chaperone in human cerebrospinal fluid. The presence of high levels of bilirubin and its derivatives, implicated in Alzheimer's disease, by binding to L-PGDS may reduce its chaperone activity. Nevertheless, our ThT binding assay establishes that heme and heme metabolites do not significantly alter the neuroprotective chaperone function of L-PGDS. Guided by NMR data we reconstructed the heme L-PGDS complex using extensive molecular dynamics simulations providing a plat...
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research