Intermolecular Electron-Transfer Reactions in Soluble Methane Monooxygenase:  A Role for Hysteresis in Protein Function

Blazyk, Jessica L.; Gassner, George; Lippard, Stephen J.

doi:10.1021/ja0554054

Cited by 29 publications

(63 citation statements)

References 73 publications

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“…An application of Marcus Theory to the electron transfer rates between MMOR Fd and MMOH estimates that the [2Fe-2S] cluster rests~11-14 Å from the dinuclear iron center [114]. This distance is consistent with theories of efficient electron transfer rates in biological systems that generally position electron donors and acceptors within 14 Å of each other [145].…”

Section: Reductase Binding and Effects On The Hydroxylasesupporting

confidence: 62%

Methane Monooxygenase: Functionalizing Methane at Iron and Copper

Sazinsky

Lippard

2014

Sustaining Life on Planet Earth: Metalloenzymes Mastering Dioxygen and Other Chewy Gases

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Methane monooxygenases (MMOs) catalyze the conversion of methane to methanol as the first committed step in the assimilation of this hydrocarbon into biomass and energy by methanotrophs, thus playing a significant role in the biogeochemistry of this potent greenhouse gas. Two distinct enzymes, a copper-dependent membrane protein, particulate methane monooxygenase (pMMO), and an iron-dependent cytosolic protein, soluble methane monooxygenase (sMMO), carry out this transformation using large protein scaffolds that help to facilitate the timely transport of hydrocarbon, O₂, proton, and electron substrates to buried dimetallic active sites. For both enzymes, reaction of the reduced metal centers with O₂leads to intermediates that activate the relatively inert C-H bonds of hydrocarbons to yield oxidized products. Among synthetic and biological catalysts, MMOs are unique because they are the only ones known to hydroxylate methane at ambient temperatures. As a need for new industrial catalysts and green chemical transformations increases, understanding how the different MMO metal centers efficiently accomplish this challenging chemistry has become the focus of intense study. This chapter examines current understanding of the sMMO and pMMO protein structures, their methods for substrate channeling, and mechanisms for the dimetallic activation of O₂and C-H bonds.

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Section: Reductase Binding and Effects On The Hydroxylasesupporting

confidence: 62%

Methane Monooxygenase: Functionalizing Methane at Iron and Copper

Sazinsky

Lippard

2014

Sustaining Life on Planet Earth: Metalloenzymes Mastering Dioxygen and Other Chewy Gases

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“…Thus, a long-lived conformational change in the hydroxylase has been invoked to explain the several documented effects of effector protein binding. Long-lived conformational changes have also been proposed to explain the effects of methane monooxygenase reductase on single turnover rates, redox potentials, and O 2 activation (6,22).…”

Section: Resultsmentioning

confidence: 99%

Structural consequences of effector protein complex formation in a diiron hydroxylase

Bailey

McCoy

Phillips

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

201

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Carboxylate-bridged diiron hydroxylases are multicomponent enzyme complexes responsible for the catabolism of a wide range of hydrocarbons and as such have drawn attention for their mechanism of action and potential uses in bioremediation and enzymatic synthesis. These enzyme complexes use a small molecular weight effector protein to modulate the function of the hydroxylase. However, the origin of these functional changes is poorly understood. Here, we report the structures of the biologically relevant effector protein-hydroxylase complex of toluene 4-monooxygenase in 2 redox states. The structures reveal a number of coordinated changes that occur up to 25 Å from the active site and poise the diiron center for catalysis. The results provide a structural basis for the changes observed in a number of the measurable properties associated with effector protein binding. This description provides insight into the functional role of effector protein binding in all carboxylate-bridged diiron hydroxylases.crystal structure ͉ iron enzyme ͉ mechanism ͉ oxygenase C arboxylate-bridged diiron enzymes provide essential biological functions such as O 2 transport, iron sequestration, deoxyribonucleotide synthesis, fatty acid desaturation, and hydrocarbon hydroxylation (1). All diiron hydroxylase complexes include a multisubunit hydroxylase, electron transfer proteins, and a cofactorless effector protein that is unique to the diiron hydroxylase family (2). Effector proteins are required for catalysis, and their presence is associated with improved coupling (3), shifts in redox potential (4), increased rate of catalysis (3), more efficient activation of O 2 (5), and changes in regiospecificity (3, 6). Correlation of how the effector protein may induce these phenomena ultimately requires examination of high-resolution structures of the stoichiometric protein-protein complexes in multiple redox states. Previously available structures with smallmolecule analogs (7,8) or partial occupancy of an effector protein binding site (9) have provided some insight into regions of the hydroxylase that might be perturbed by these interactions. Surprisingly, however, changes in the active site were not observed, although these might reasonably be anticipated based on numerous spectroscopic studies of this enzyme family (10). Consequently, further information is needed to better understand the role of effector protein binding in catalysis by diiron hydroxylases.Toluene 4-monooxygenase (T4moH*; 200 kDa) is composed of TmoA, TmoE, and TmoB polypeptides and has an (␣␤␥) 2 quaternary structure (11). This enzyme hydroxylates toluene with high regiospecificity in the presence of its effector protein, T4moD (3, 12). Here, we report X-ray structures of resting T4moH, the stoichiometric complex of resting T4moH with T4moD, and the sodium dithionite-reduced complex to resolutions of 1.9, 1.9, and 1.7 Å respectively [see supporting information (SI) Table S1 for refinement statistics]. Comparison of these structures revealed changes within the active site and ...

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“…However, systematic similarities between the sMMO and other diiron oxygenases, for which the mechanism is well understood [41], allow one to propose several hypotheses on the transport of electrons inside the sMMO [42].…”

Section: Methane Monooxygenasementioning

confidence: 99%