HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ator, M. A. Articles by Ortiz de Montellano, P. R. Search for Related Content PubMed PubMed Citation Articles by Ator, M. A. Articles by Ortiz de Montellano, P. R. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 262, Issue 31, 14954-14960, Nov, 1987

Structure and catalytic mechanism of horseradish peroxidase. Regiospecific meso alkylation of the prosthetic heme group by alkylhydrazines

MA Ator, SK David and PR Ortiz de Montellano
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143.

Horseradish peroxidase is inactivated in a time-, H2O2-, and concentration-dependent manner by phenylethyl-, ethyl-, and methylhydrazine. The pseudo- first order kinetic constants for these inactivation reactions at pH 7 are: phenylethyl (KI = 115 microM, kinact = 1.5 min-1, partition ratio = 11), ethyl (KI = 145 microM, kinact = 0.08 min-1, partition ratio = 32), and methyl (KI = 3000 microM, kinact = 0.12 min-1, partition ratio = 80). At pH 5, the constants for the phenylethyl reaction change to KI = 1540 microM and kinact = 0.86 min-1. A transient absorbance at approximately 830 nm, suggestive of an isoporphyrin intermediate, is seen during these reactions. The prosthetic heme is converted by each of the three alkylhydrazines into the corresponding delta-meso-alkylated heme. Complete inactivation of the enzymes by methyl-, ethyl-, and phenylethylhydrazine is associated with alkylation of 60-70, 70, and 90%, respectively, of the prosthetic heme groups. The absence of N- alkylation and the high specificity for the delta-meso position, even with agents as small as methylhydrazine, strengthen the proposal that electron abstraction is mediated by the heme edge rather than the ferryl oxygen of horseradish peroxidase.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. M. Vyas, S. Roychowdhury, S. B. Koukouritaki, R. N. Hines, S. K. Krueger, D. E. Williams, W. M. Nauseef, and C. K. Svensson Enzyme-Mediated Protein Haptenation of Dapsone and Sulfamethoxazole in Human Keratinocytes: II. Expression and Role of Flavin-Containing Monooxygenases and Peroxidases J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 497 - 505. [Abstract] [Full Text] [PDF]

				V. Trivedi, P. Chand, K. Srivastava, S. K. Puri, P. R. Maulik, and U. Bandyopadhyay Clotrimazole Inhibits Hemoperoxidase of Plasmodium falciparum and Induces Oxidative Stress: PROPOSED ANTIMALARIAL MECHANISM OF CLOTRIMAZOLE J. Biol. Chem., December 16, 2005; 280(50): 41129 - 41136. [Abstract] [Full Text] [PDF]

				J. L. Vuletich, E. R. Lowe, S. Jianmongkol, Y. Kamada, U. M. Kent, A. T. Bender, D. R. Demady, P. F. Hollenberg, and Y. Osawa Alteration of the Heme Prosthetic Group of Neuronal Nitric-Oxide Synthase during Inactivation by NG-Amino-L-arginine in Vitro and in Vivo Mol. Pharmacol., July 1, 2002; 62(1): 110 - 118. [Abstract] [Full Text] [PDF]

				S. Jianmongkol, J. L. Vuletich, A. T. Bender, D. R. Demady, and Y. Osawa Aminoguanidine-mediated Inactivation and Alteration of Neuronal Nitric-oxide Synthase J. Biol. Chem., April 28, 2000; 275(18): 13370 - 13376. [Abstract] [Full Text] [PDF]

				M. I. Savenkova, S. L. Newmyer, and P. R.O. d. Montellano Rescue of His-42 right-arrow Ala Horseradish Peroxidase by a Phe-41 right-arrow His Mutation. ENGINEERING OF A SURROGATE CATALYTIC HISTIDINE J. Biol. Chem., October 4, 1996; 271(40): 24598 - 24603. [Abstract] [Full Text] [PDF]

				S. L. Newmyer and P. R.O. d. Montellano Rescue of the Catalytic Activity of an H42A Mutant of Horseradish Peroxidase by Exogenous Imidazoles J. Biol. Chem., June 21, 1996; 271(25): 14891 - 14896. [Abstract] [Full Text] [PDF]

				S. L. Newmyer and P. R. O. de Montellano Horseradish Peroxidase His-42 [IMAGE] Ala, His-42 [IMAGE] Val, and Phe-41 [IMAGE] Ala Mutants J. Biol. Chem., August 18, 1995; 270(33): 19430 - 19438. [Abstract] [Full Text] [PDF]

				J. Dawson Probing structure-function relations in heme-containing oxygenases and peroxidases Science, April 22, 1988; 240(4851): 433 - 439. [Abstract] [PDF]

				C. Colas, J. M. Kuo, and P. R. O. de Montellano Asp-225 and Glu-375 in Autocatalytic Attachment of the Prosthetic Heme Group of Lactoperoxidase J. Biol. Chem., February 22, 2002; 277(9): 7191 - 7200. [Abstract] [Full Text] [PDF]