Crystal structure of guaiacol and phenol bound to a heme peroxidase
Open Access
- 16 November 2011
- journal article
- Published by Wiley in The FEBS Journal
- Vol. 279 (9), 1632-1639
- https://doi.org/10.1111/j.1742-4658.2011.08425.x
Abstract
Guaiacol is a universal substrate for all peroxidases, and its use in a simple colorimetric assay has wide applications. However, its exact binding location has never been defined. Here we report the crystal structures of guaiacol bound to cytochrome c peroxidase (CcP). A related structure with phenol bound is also presented. The CcP–guaiacol and CcP–phenol crystal structures show that both guaiacol and phenol bind at sites distinct from the cytochrome c binding site and from the δ-heme edge, which is known to be the binding site for other substrates. Although neither guaiacol nor phenol is seen bound at the δ-heme edge in the crystal structures, inhibition data and mutagenesis strongly suggest that the catalytic binding site for aromatic compounds is the δ-heme edge in CcP. The functional implications of these observations are discussed in terms of our existing understanding of substrate binding in peroxidases [Gumiero A et al. (2010) Arch Biochem Biophys500, 13–20].Keywords
This publication has 40 references indexed in Scilit:
- Mode of Binding of the Tuberculosis Prodrug Isoniazid to Heme PeroxidasesOnline Journal of Public Health Informatics, 2010
- Binding Modes of Aromatic Ligands to Mammalian Heme Peroxidases with Associated Functional Implications: CRYSTAL STRUCTURES OF LACTOPEROXIDASE COMPLEXES WITH ACETYLSALICYLIC ACID, SALICYLHYDROXAMIC ACID, AND BENZYLHYDROXAMIC ACIDOnline Journal of Public Health Informatics, 2009
- Inhibition of Lactoperoxidase by Its Own Catalytic Product: Crystal Structure of the Hypothiocyanate-Inhibited Bovine Lactoperoxidase at 2.3-Å ResolutionBiophysical Journal, 2009
- Engineering the Substrate Specificity and Reactivity of a Heme Protein: Creation of an Ascorbate Binding Site in Cytochrome c PeroxidaseBiochemistry, 2008
- Probing Molecular Docking in a Charged Model Binding SiteJournal of Molecular Biology, 2006
- Coot: model-building tools for molecular graphicsActa crystallographica. Section D, Structural biology, 2004
- Crystal structure of the ascorbate peroxidase–ascorbate complexNature Structural & Molecular Biology, 2003
- Refinement of Macromolecular Structures by the Maximum-Likelihood MethodActa crystallographica. Section D, Structural biology, 1997
- Solution Characterisation by NMR Spectroscopy of Two Horseradish Peroxidase Isoenzyme C Mutants with Alanine Replacing Either Phe142 or Phe143JBIC Journal of Biological Inorganic Chemistry, 1995
- The CCP4 suite: programs for protein crystallographyActa crystallographica. Section D, Structural biology, 1994