Aromatic substrate molecules bind at the distal heme pocket of myeloperoxidase

Hiroshi Hori, Roger E. Fenna, Shioko Kimura, Masao Ikeda-Saito

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60 Citations (Scopus)

Abstract

Binding of aromatic substrate molecules to myeloperoxidase has been investigated by EPR spectroscopy and model building. Binding of aromatic substrate molecules, such as phenol, p-cresol, resorcinol, and 4-amino salicylate, replaces the original rhombic high spin EPR spectrum of the ferric enzyme (g = 6.74, 5.18, and 1.97) by another high spin signal (g = 7.04, 4.87, and 1.93) indicating that these substrate molecules bind near the heme center of the enzyme. Salicylhydroxamic acid and benzohydroxamic acid complexes of myeloperoxidase showed EPR spectra composed of high spin (g = 6.99, 4.93, and 1.95) and low spin (2.66, 2.22, and 1.81) signals. The hydroxamic side chains of these two substrates seem to interact with the heme iron. Model building based on the three-dimensional structure of the enzyme (Zeng, J., and Fenna, R. E. (1992) J. Mol. Biol. 226, 185-207) revealed the presence of a hydrophobic pocket at the entrance of the distal heme cavity where the aromatic ring of these substrates can bind. Moreover, the six- membered ring portion of salicylhydroxamic acid and benzohydroxamic acid could bind to this hydrophobic pocket with the hydroxamic side chain placed between the imidazole of the distal His and the heme iron. The EPR results on lactoperoxidase and intestinal peroxidase also suggest the presence of an aromatic substrate binding site similar to that of myeloperoxidase.

Original languageEnglish
Pages (from-to)8388-8392
Number of pages5
JournalJournal of Biological Chemistry
Volume269
Issue number11
Publication statusPublished - 1994 Mar 18

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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