A Tour of Methane Monooxygenase

Please be patient while the structures in the left frame load. In order to display all of the structures in the tour properly, press 'View' buttons below in order (from 1 to the end).

This is a display of the hydroxylase part of methane monooxygenase from the bacterium methylococcus capsulatus. The hydroxylase component is the largest of the three proteins; it has a molecular weight of 245 Kdaltons. A monooxygenase transfers one oxygen atom from dioxygen onto the substrate. The substrate in this case is methane.
CH4 + O2 + H+ + NADH
                                    CH3OH + H2O + NAD+

These enzymes are found in bacteria, called methanotrophs, that use methane as a source of energy and carbon. The structure of methane monooxygenase consists of three proteins, a reductase, a regulator, and a hydroxylase.

Only the hydroxylase is shown here. It exists in a dimeric form. In this display there is a vertical two-fold axis down the center of the screen. This enzyme is almost completely composed of alpha- helices. There is a wide canyon formed between the dimer.

Alpha helices are coloured in blue and beta-sheets are coloured in red.

Only one half of the hydroxylase is represented here in red, blue, and green. The red section is the alpha subunit, which contains the diiron cluster. The blue is the beta subunit and the green is the gamma subunit. The other half is identical.

This is a display of the spacefilled monomer of methane monooxygenase hydroxylase. The hydrophobic residues have been highlighted in red. Five amino acid residues have been shown as wireframe in order for the diiron center to be shown more clearly. These residues in wireframe are hydrophilic Glu, Asp and His. The most hydrophobic region has been labelled. Methane migrates through this cavity in order to bind to the active site. (Restart the rotation.)

Fe1 is coordinated to two carboxylate groups from Glu, one imidazole ring from His, a water molecule, a bridging acetate and hydroxide ion. Fe1 has an octahedral coordination geometry. Fe2 on the other hand is only coordinated to five ligands. All the ligands are the same except that Fe2 is not coordinated to the water molecule. Bond distances for the water molecule - Fe1 and for the hydroxo bridge are shown.

This display emphasizes the unsymmetrical interaction of the carboxylate ligand. The mechanism involved in the hydroxylation of a C-H bond of methane begins with O2 binding to the diferrous state to give a diferric 2Fe(III) center containing a peroxide (O22-) ligand which is probably bridging. This is then converted to water and probably an Fe(IV)-oxo species which abstracts a hydrogen atom from methane to produce an Fe(III)-hydroxide. The methyl radical combines with this hydroxide to form the product methanol.

This is MMO for you to explore further.

The crystal structure of methane monooxygenase was reported by Rosenzweig et al. in Nature 1993, 366, 537.

Copyright Robert H. Morris, Adrian Lee and Alen Hadzovic, 1998, 2009

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The Guided Tours of Metalloproteins by Alen Hadzovic and Robert H. Morris is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License