Structure methane monooxygenase

Intermediates in the reaction cycle of methane monooxygenase structure and chemistry... 

Enzymes necessary for the metabolism of a substrate may be induced by growth on structurally unrelated compounds. In the examples used for illustration, monooxygenases play a cardinal role as a result of the versatility of methane monooxygenase, while monooxygenases that may be involved in toluene degradation are discussed in Chapter 3, Part 1 and Chapter 8, Part 1. 

STUDIES OF THE SOLUBLE METHANE MONOOXYGENASE PROTEIN SYSTEM STRUCTURE, COMPONENT INTERACTIONS, AND HYDROXYLATION MECHANISM... 

Metalloenzymes with non-heme di-iron centers in which the two irons are bridged by an oxide (or a hydroxide) and carboxylate ligands (glutamate or aspartate) constitute an important class of enzymes. Two of these enzymes, methane monooxygenase (MMO) and ribonucleotide reductase (RNR) have very similar di-iron active sites, located in the subunits MMOH and R2 respectively. Despite their structural similarity, these metal centers catalyze very different chemical reactions. We have studied the enzymatic mechanisms of these enzymes to understand what determines their catalytic activity [24, 25, 39-41]. 

Figure 13.25 Three-dimensional structures of diiron proteins. The iron-binding subunits of (a) haemery-thrin, (b) bacterioferritin, (c) rubryerythrin (the FeS centre is on the top), (d) ribonucleotide reductase R2 subunit, (e) stearoyl-acyl carrier protein A9 desaturase, (f) methane monooxygenase hydroxylase a-subunit. (From Nordlund and Eklund, 1995. Copyright 1995, with permission from Elsevier.)...

Studies of the Soluble Methane Monooxygenase Protein System Structure, Component Interactions, and Hydroxylation Mechanism Katherine E. Liu and Stephen J. Lippard... 

It seems probable that other redox centres contain this binuclear iron structure, but that this has not yet been recognized. For example, a non-heme iron protein of the methane monooxygenase from Methylococcus capsulatus (Bath), which functions as the oxygenase in equation (28), has been described as having a novel iron centre which is not an iron-sulfur cluster. This may well be an oxo-bridged system. Analysis suggests 2.3 Fe per molecule of protein. 

Lieberman, R. L. Rosenzweig, A. C. Biological methane oxidation regulation, biochemistry, and active site structure of particulate methane monooxygenase. Crit. Rev. Biochem. Mol. Biol. 2004, 39(3), 147-164. 

Kitmitto, A. Myronova, N. Basu, R Dalton, H. Characterization and structural analysis of an active particulate methane monooxygenase trimer from Methylococcus capsulatus (Bath). Biochemistry 2005, 44(33), 10954-10965. 

Shu LJ, Nesheim JC, Kauffmann K, Miinck E, Lipscomb JD, Que L. An Fe2IV02 diamond core structure for the key intermediate Q of methane monooxygenase. Science. 1997 275 515-8. 

First two complexes with a (p.-oxo)(p-hydroxo)diiron (III) core [Fe2(0)(0H)(6TLA)2(C104)3] (I) and [Fe2(0)2(6TLA)2(C104)2] (II), were isolated and characterized (Zang et al 1995). Structure of a (-l,2-peroxo)bis(-carboxylato)diiron(m)model for the peroxo intermediate in the methane monooxygenase hydroxylase reaction cycle is presented in Fig, 6.3. 

Figure 6..3.. Structure of a (-l,2-peroxo)bis(-carboxylato)diiron(III)model for the peroxo intermediate in the methane monooxygenase hydroxylase (Zang et al., 1995) Reproduced with permission.

Muller, J., Lugovskoy, A. A., Wagner, G., and Lippard, S.J. (2002) NMR structure of the [2Fe-2S] ferredoxin domain from soluble methane monooxygenase reductase and interaction with its hydroxylase. Biochemistry 41, 42-51. 

Whittington, D.A., Sazinsky, M.H., and Lippard, S J. (2001) X-ray Crystal Structure of Alcohol Products Bound at the Active Site of Soluble Methane Monooxygenase Hydroxylase. J. Am. Chem. Soc, 123, 1794-... 

However, it is possible to detect a tyrosine radical optically in ribonucleotide reductase, as there is only a relatively weak competing absorption from the binuclear non-haem iron centre [164]. A distinct sharp peak is seen that is not present in proteins that have been treated with the radical scavenger hydroxyurea [165,166] nor is it present in proteins such as haemerythrin or methane monooxygenase, which have similar active-site structures, but lack... 

Some preparations of iron exchanged into zeolite H-MFI by vapor-phase FeCL are known to be active and selective catalysts for the reduction of NO, with hydrocarbons or ammonia in the presence of excess oxygen and water vapor (45,46). The active centers in Fe/MFI are assumed to be binuclear, oxygen-bridged iron complexes, as follows from H2-TPR, CO-TPR, and ESR data (45,47) and EXAFS and XANES results (48,49). These complexes are structurally similar to the binuclear iron centers in methane monooxygenase enzymes that are employed by methanotrophic bacteria in utilization of methane as their primary energy source (50). It is believed that molecular oxygen reacts with these centers to form peroxide as the initial step in this chemistry (50). 

Chang, S. L., Wallar, B. J., Lipscomb, J. D., and Mayo, K. H., 1999, Solution structure of component B from methane monooxygenase derived through heteronuclear NMR and molecular modeling, Biochemistry 38 5799n5812. 

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