Volume 272, Number 14, Issue of April 4, 1997 pp. 8857-8860
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

---

COMMUNICATION:
Autocatalytic Processing of Heme by Lactoperoxidase Produces the Native Protein-bound Prosthetic Group

(Received for publication, November 6, 1996, and in revised form, February 12, 1997)

From the Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, California 94143-0446

The covalently bound prosthetic group of lactoperoxidase (LPO) has been obtained by hydrolysis of the protein and identified as a dihydroxylated heme. A baculovirus expression system has been developed for LPO and used to obtain protein in which the heme is only partially covalently bound. Reaction of the purified heme·apoLPO complex with H₂O₂ results in both autocatalytic modification of the heme and covalent attachment to the protein. Hydrolytic experiments establish that the autocatalytically incorporated heme is bound normally. Two monohydroxylated heme intermediates have been detected. The peroxidative activity of LPO increases in proportion to the extent of covalently bound heme. The LPO results provide a paradigm for autocatalytic incorporation of heme groups into the mammalian peroxidases, including myeloperoxidase and eosinophil peroxidase, all of which exhibit strong sequence similarity with LPO and have covalently-bound heme groups.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Goedken, S. McCormick, K. G. Leidal, K. Suzuki, Y. Kameoka, J. M. Astern, M. Huang, A. Cherkasov, and W. M. Nauseef Impact of Two Novel Mutations on the Structure and Function of Human Myeloperoxidase J. Biol. Chem., September 21, 2007; 282(38): 27994 - 28003. [Abstract] [Full Text] [PDF]

				W. Liu, C. E. Rogge, B. Bambai, G. Palmer, A.-L. Tsai, and R. J. Kulmacz Characterization of the Heme Environment in Arabidopsis thaliana Fatty Acid {alpha}-Dioxygenase-1 J. Biol. Chem., July 9, 2004; 279(28): 29805 - 29815. [Abstract] [Full Text] [PDF]

				C. Colas and P. R. O. de Montellano Horseradish Peroxidase Mutants That Autocatalytically Modify Their Prosthetic Heme Group: INSIGHTS INTO MAMMALIAN PEROXIDASE HEME-PROTEIN COVALENT BONDS J. Biol. Chem., June 4, 2004; 279(23): 24131 - 24140. [Abstract] [Full Text] [PDF]

				C. Ciaccio, G. De Sanctis, S. Marini, F. Sinibaldi, R. Santucci, A. Arcovito, A. Bellelli, E. Ghibaudi, P. Ferrari Rosa, and M. Coletta Proton Linkage for CO Binding and Redox Properties of Bovine Lactoperoxidase Biophys. J., January 1, 2004; 86(1): 448 - 454. [Abstract] [Full Text] [PDF]

				L. A. LeBrun, U. Hoch, and P. R. Ortiz de Montellano Autocatalytic Mechanism and Consequences of Covalent Heme Attachment in the Cytochrome P4504A Family J. Biol. Chem., April 5, 2002; 277(15): 12755 - 12761. [Abstract] [Full Text] [PDF]

				T. J. Fiedler, C. A. Davey, and R. E. Fenna X-ray Crystal Structure and Characterization of Halide-binding Sites of Human Myeloperoxidase at 1.8 A Resolution J. Biol. Chem., April 14, 2000; 275(16): 11964 - 11971. [Abstract] [Full Text] [PDF]

				O. M. Lardinois, K. F. Medzihradszky, and P. R. O. de Montellano Spin Trapping and Protein Cross-linking of the Lactoperoxidase Protein Radical J. Biol. Chem., December 10, 1999; 274(50): 35441 - 35448. [Abstract] [Full Text] [PDF]

				I. M. Kooter, N. Moguilevsky, A. Bollen, L. A. van der Veen, C. Otto, H. L. Dekker, and R. Wever The Sulfonium Ion Linkage in Myeloperoxidase. DIRECT SPECTROSCOPIC DETECTION BY ISOTOPIC LABELING AND EFFECT OF MUTATION J. Biol. Chem., September 17, 1999; 274(38): 26794 - 26802. [Abstract] [Full Text] [PDF]

				C. Oxvig, A. R. Thomsen, M. T. Overgaard, E. S. Sorensen, P. Hojrup, M. J. Bjerrum, G. J. Gleich, and L. Sottrup-Jensen Biochemical Evidence for Heme Linkage through Esters with Asp-93 and Glu-241 in Human Eosinophil Peroxidase. THE ESTER WITH ASP-93 IS ONLY PARTIALLY FORMED IN VIVO J. Biol. Chem., June 11, 1999; 274(24): 16953 - 16958. [Abstract] [Full Text] [PDF]

				L. Fayadat, P. Niccoli-Sire, J. Lanet, and J.-L. Franc Role of Heme in Intracellular Trafficking of Thyroperoxidase and Involvement of H2O2 Generated at the Apical Surface of Thyroid Cells in Autocatalytic Covalent Heme Binding J. Biol. Chem., April 9, 1999; 274(15): 10533 - 10538. [Abstract] [Full Text] [PDF]

				T. D. Rae and H. M. Goff The Heme Prosthetic Group of Lactoperoxidase. STRUCTURAL CHARACTERISTICS OF HEME l AND HEME l-PEPTIDES J. Biol. Chem., October 23, 1998; 273(43): 27968 - 27977. [Abstract] [Full Text] [PDF]

				W. M. Nauseef, S. J. McCormick, and M. Goedken Coordinated Participation of Calreticulin and Calnexin in the Biosynthesis of Myeloperoxidase J. Biol. Chem., March 20, 1998; 273(12): 7107 - 7111. [Abstract] [Full Text] [PDF]

				J. Guo, S. M. McLachlan, S. Hutchison, and B. Rapoport The Greater Glycan Content of Recombinant Human Thyroid Peroxidase of Mammalian Than of Insect Cell Origin Facilitates Purification to Homogeneity of Enzymatically Protein Remaining Soluble at High Concentration Endocrinology, March 1, 1998; 139(3): 999 - 1005. [Abstract] [Full Text] [PDF]

				U. Hoch and P. R. Ortiz de Montellano Covalently Linked Heme in Cytochrome P4504A Fatty Acid Hydroxylases J. Biol. Chem., March 30, 2001; 276(14): 11339 - 11346. [Abstract] [Full Text] [PDF]

				F. Pacello, P. R. Langford, J. S. Kroll, C. Indiani, G. Smulevich, A. Desideri, G. Rotilio, and A. Battistoni A Novel Heme Protein, the Cu,Zn-Superoxide Dismutase from Haemophilus ducreyi J. Biol. Chem., August 3, 2001; 276(32): 30326 - 30334. [Abstract] [Full Text] [PDF]

				O. M. Lardinois and P. R. O. de Montellano H2O2-mediated Cross-linking between Lactoperoxidase and Myoglobin. ELUCIDATION OF PROTEIN-PROTEIN RADICAL TRANSFER REACTIONS J. Biol. Chem., June 15, 2001; 276(25): 23186 - 23191. [Abstract] [Full Text] [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]