5wv3

Publication Abstract from PubMed

The mammalian heme peroxidases including lactoperoxidase (LPO), myeloperoxidase (MPO), eosinophil peroxidase (EPO) and thyroid peroxidase (TPO) contain a covalently linked heme moiety. Initially, it was believed that the heme group was fully cross-linked to protein molecule through at least two ester linkages involving conserved glutamate and aspartate residues with 1-methyl and 5-methyl groups of pyrrole rings A and C respectively. In MPO, an additional sulfonium ion linkage was present between 2-vinyl group of pyrrole ring A of the heme moiety and a methionine residue of the protein. These linkages were formed through a self processing mechanism. Subsequently, biochemical studies indicated that the heme moiety was partially attached to protein. The recent structural studies have shown that the covalent linkage involving glutamate and 1-methyl group of pyrrole ring of heme moiety was partially formed. When glutamate is not covalently linked to heme moiety, its side chain occupies a position in the substrate binding site on the distal heme side and blocks the substrate binding site leading to inactivation. However, an exposure to H2O2 converts it to a fully covalently linked state with heme. Thus in mammalian heme peroxidases, the Glu-heme linkage is essential for catalytic action.

Structural basis of activation of mammalian heme peroxidases.,Singh PK, Iqbal N, Sirohi HV, Bairagya HR, Kaur P, Sharma S, Singh TP Prog Biophys Mol Biol. 2018 Mar;133:49-55. doi: 10.1016/j.pbiomolbio.2017.11.003., Epub 2017 Nov 22. PMID:29174286^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.