Copper methane monooxygenase

Nguyen H-HT, AK Shiemka, S J Jacobs, BJ Hales, ME Lidstrom, S 1 Chan (1994) The nature of the copper ions in the membranes containing the particulate methane monooxygenase from Methylococcus capsu-latus (Bath). J Biol Chem 269 14995-15005. 

Methane monooxygenase may exist in either soluble (sMMO) or particulate (pMMO) forms. These display different substrate ranges and different rates of transformation rates, and most methanotrophs express only the latter form of the enzyme (Hanson and Hanson 1996). The particulate form of methane monooxygenase contains copper, or both copper... 

H. H. T. Nguyen, S. J. Elliott, J. H. K. Yip, S. I. Chan (1998) The particulate methane monooxygenase from Methylococcus capsulatus (Bath) is a novel copper-containing three-subunit enzyme - Isolation and characterization. J. Biol. Chem., 273 7957-7966... 

Two types of methane monooxygenases have been studied (1) soluble methane monooxygenase (sMMO) and (2) particulate (membrane-bound) methane monooxygenase (pMMO). The well-studied sMMO is produced by methanotrophs under copper-limiting conditions. All methanotrophs produce pMMO—found in intracytoplasmic membranes— but it is the less well-studied enzyme. 

Solid-state supramolecular complexes, see Su-pramolecular copper(l)/silver(I) complexes Solubility products, 17 215 Soluble methane monooxygenase protein system, 42 263-286 hydroxylation... 

Usually, these metalloproteins contain both type 2 and type 3 copper centers, together forming a triangular-shaped trinuclear active site, such as found in laccase (polyphenol oxidase) [38-41] and ascorbate oxidase (3) [42]. Recent evidence for a related arrangement has been reported for the enzyme particulate methane monooxygenase as well [43], but in this case the Cu Cu distance of the type 2 subunit (2.6 A) appears to be unusually short and the third Cu ion is located far from the dinuclear site. 

The multiprotein complex methane monooxygenase (MMO) serves meth-anotrophs to convert methane to methanol. It can be either soluble (sMMO) or membrane bound ( particulate , pMMO) and it typically consists of three components, a reductase (MMOR), a component termed protein B (MMOB) and a hydroxylase denoted MMOH. The nature of the metal cofactors in the latter component are reasonably well understood for sMMO as will be discussed in the non-heme iron section. For the pMMO of Methylococcus capsulatus an obligate requirement for copper was shown. As reported in reference 1 a trinuclear Cu(II) cluster was discussed128 but the number and coordination of coppers still is a matter of continuing investigation since then. 

Phelps, P. A., Agarwal, S. K., Speitel, G. E., Jr Georgiou, G. (1992). Methylosinus trichosporium OB3b mutants having constitutive expression of soluble methane monooxygenase in the presence of high levels of copper. Applied and Environmental Microbiology, 58, 3701-8. 

Lieberman, R. L. Shrestha, D. B. Doan, P. E. Hoffman, B. M. Stemmier, T. L. Rosenzweig, A. C. Purified particulate methane monooxygenase from Methylococcus capsulatus (Bath) is a dimer with both mononuclear copper and a copper-containing cluster. Proc. Natl. Acad. Sci. USA 2003, 100(1), 3820-3825. 

Nguyen, H. H., Nakagawa, K. H., Hedman, B., Elliott, S. J., Lidstrom, M. E., Hodgson, K. O., and Chan, S. L, 1996, X-ray absorption and EPR studies on the copper ions associated with the particulate methane monooxygenase from Methylococcus capsulatus (Bath)6 Cu(I) Ions and their implications, J. Am. Chem. Soc. 118 12766nl2776. 

Stanley, S. H., Prior, S. D., I ak, D. J., and Dalton, H., 1983, Copper stress underlies the fundamental change in intracellular location of methane monooxygenase in methane-oxidizing organisms Studies in batch and continuous cultures. Biotech. Lett. 55 487n492. 

Additional intense pre-edge features can be observed for other first-row transition metals. In cuprous containing systems, this feature arises from the Is 4p transition. As with the Is 3d transition, the intensity of the Is 4p transition depends on the coordination number and symmetry of the cuprous metal site. " A weak Is 3d transition can also be observed for cupric systems. Our laboratory has successfully applied the methodology of quantitating both Is 3d and the Is 4p transition areas to elucidate the complex mixed valence copper environment in the multicopper active sites in particulate methane monooxygenase. ... 

Figure 3 Illustration of possible partial reaction cycles of some oxygenase enzymes. Water molecules and protein ligands have sometimes been omitted for clarity, (a) P450 (18) (b) intradiol dioxygenase (7) (c) lipoxygenase (7) (d) a-KG-dependent non-heme Iron enzymes (14) (e) soluble methane monooxygenase (15) (f) uncoupled blnuclear copper (16) (g) coupled blnuclear copper (h) flavin monooxygenases (17).

Methane is oxidized under aerobic conditions by a group of bacteria called methanotrophs. These widespread bacteria play an important role in the global cycling of methane. Two types of methane oxidation systems are known, a ubiquitous particulate methane monooxygenase (pMMO) and a cytoplasmic soluble methane monooxygenase (sMMO) found in only a few strains. These enzymes have different catalytic characteristics, and so it is important to know the conditions under which each is expressed. In those strains containing both sMMO and pMMO, the available copper concentration controls which enzyme is expressed. However, the activity of the pMMO is also affected by copper. Data on methane oxidation in natural samples suggest that methanotrophs are not copper-limited in nature and express the pMMO predominantly. 

Methanotrophs are Gram-negative bacteria which utilise methane as their sole source of carbon and energy. They play an important role in controlling emissions of CH4, the second most important greenhouse gas after CO2. Almost aU methanotrophs use a copper-dependent methane monooxygenase in the first step of carbon... 

Himes, R. A., Karlin, K. D. (2009). Copper-dioxygen complex mediated C—H bond oxygenation relevance for particulate methane monooxygenase (pMMO). Current Opinion in Chemical Biology, 13, 119—131. 

Function. An obvious function of methane monooxygenase is the oxidation of methane to methanol. The membrane-bound form could fulfill this function within an electron-transport chain. A further, possible function could be derived from the observation that, in methanotrophic bacteria grown in copper-enriched medium, the main mass of membrane-bound proteins is methane... 

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