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

J. Biol. Chem., Vol. 278, Issue 36, 34654-34659, September 5, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/36/34654    most recent M302985200v1 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 Friedman, J. Articles by Poulos, T. L. Search for Related Content PubMed PubMed Citation Articles by Friedman, J. Articles by Poulos, T. L. Social Bookmarking                      What's this?

Crystal Structures of the NO- and CO-bound Heme Oxygenase from Neisseriae meningitidis

IMPLICATIONS FOR O₂ ACTIVATION^*

Jonathan Friedman , Latesh Lad , Rahul Deshmukh , Huiying Li , Angela Wilks  and Thomas L. Poulos  ¶

From the Department of Molecular Biology and Biochemistry, Department of Physiology and Biophysics, and Program in Macromolecular Structure, University of California, Irvine, California 92697 and Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201

Heme oxygenases catalyze the oxidation of heme to biliverdin, carbon monoxide, and free iron while playing a critical role in mammalian heme homeostasis. Pathogenic bacteria such as Neisseriae meningitidis also produce heme oxygenase as part of a mechanism to mine host iron. The key step in heme oxidation is the regioselective oxidation of the heme -meso-carbon by an activated Fe(III)-OOH complex. The structures of various diatomic ligands bound to the heme iron can mimic the dioxygen complex and provide important insights on the mechanism of O₂ activation. Here we report the crystal structures of N. meningitidis heme oxygenase (nm-HO) in the Fe(II), Fe(II)-CO, and Fe(II)-NO states and compare these to the NO complex of human heme oxygenase-1 (Lad, L., Wang, J., Li, H., Friedman, J., Bhaskar, B., Ortiz de Montellano, P. R., and Poulos, T. L. (2003) J. Mol. Biol. 330, 527–538). Coordination of NO or CO results in a reorientation of Arg-77 that enables Arg-77 to participate in an active site H-bonded network involving a series of water molecules. One of these water molecules directly H-bonds to the Fe(II)-linked ligand and very likely serves as the proton source required for oxygen activation. Although the active site residues differ between nm-HO and human HO-1, the close similarity in the H-bonded water network suggests a common mechanism shared by all heme oxygenases.

Received for publication, March 24, 2003 , and in revised form, June 18, 2003.

The atomic coordinates and structure factors (codes 1P3T, 1P3U, and IP3V) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported by National Institutes of Health Grants GM33688 (to T. L. P.) and AI48551 (to A. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed. Tel.: 949-824-7020; Fax: 949-824-3280; E-mail: poulos{at}uci.edu.

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

This article has been cited by other articles:

				J. Friedman, Y. T. Meharenna, A. Wilks, and T. L. Poulos Diatomic Ligand Discrimination by the Heme Oxygenases from Neisseria meningitidis and Pseudomonas aeruginosa J. Biol. Chem., January 12, 2007; 282(2): 1066 - 1071. [Abstract] [Full Text] [PDF]

				M. D. L. Suits, N. Jaffer, and Z. Jia Structure of the Escherichia coli O157:H7 Heme Oxygenase ChuS in Complex with Heme and Enzymatic Inactivation by Mutation of the Heme Coordinating Residue His-193 J. Biol. Chem., December 1, 2006; 281(48): 36776 - 36782. [Abstract] [Full Text] [PDF]

				T. Matsui, M. Furukawa, M. Unno, T. Tomita, and M. Ikeda-Saito Roles of Distal Asp in Heme Oxygenase from Corynebacterium diphtheriae, HmuO: A WATER-DRIVEN OXYGEN ACTIVATION MECHANISM J. Biol. Chem., January 28, 2005; 280(4): 2981 - 2989. [Abstract] [Full Text] [PDF]

				Y. Higashimoto, H. Sakamoto, S. Hayashi, M. Sugishima, K. Fukuyama, G. Palmer, and M. Noguchi Involvement of NADP(H) in the Interaction between Heme Oxygenase-1 and Cytochrome P450 Reductase J. Biol. Chem., January 7, 2005; 280(1): 729 - 737. [Abstract] [Full Text] [PDF]

				S. Hirotsu, G. C. Chu, M. Unno, D.-S. Lee, T. Yoshida, S.-Y. Park, Y. Shiro, and M. Ikeda-Saito The Crystal Structures of the Ferric and Ferrous Forms of the Heme Complex of HmuO, a Heme Oxygenase of Corynebacterium diphtheriae J. Biol. Chem., March 19, 2004; 279(12): 11937 - 11947. [Abstract] [Full Text] [PDF]