Nonheme Diiron Centers and the Biological Oxidation of Hydrocarbons

Summary

Principal Investigator: STEPHEN LIPPARD
Affiliation: Massachusetts Institute of Technology
Country: USA
Abstract: DESCRIPTION (provided by applicant): The long-term goal of this research is to understand the activation of oxygen and subsequent selective oxidation of hydrocarbons that occurs at non-heme diiron centers in the hydroxylase enzymes of bacterial multicomponent monooxygenases (BMMs). Studies of both native and genetically modified systems, including soluble methane monooxygenase (sMMO), toluene/o-xylene monooxygenase (ToMO), and alkene monooxygenase (AMO), will enable us to elucidate the carefully orchestrated delivery of four substrates - electrons, protons, O2, and a hydrocarbon (RH) - to their diiron centers to generate product (ROH = alkyl alcohol, aryl alcohol, or epoxide) and water. Comparisons among the three enzyme systems will sharpen our understanding of features that control the nature of the oxygen activation and utilization steps. The BMMs each have several component proteins: a diiron-containing hydroxylase, an electron-donating reductase, a regulatory protein, and, in the case of ToMO, a Rieske protein. Interactions between these components will be studied to reveal features by which the monooxygenase systems control O2 activation and hydrocarbon oxidation to catalyze the selective hydroxylation or epoxidation of their respective substrates. In parallel work, synthetic model compounds will be prepared to mimic the geometric and electronic structures of the hydroxylase diiron centers. Reactions of these models with O2 and substrates will be characterized to calibrate assignments for species invoked in related enzyme chemistry. Both proteins and synthetic models will be studied by X-ray crystallography to establish geometry. Electronic, vibrational, X-ray absorption, M"ssbauer, CD/MCD, and advanced EPR techniques, some in collaboration with experts in these areas, will be applied to investigate electronic stuctures and, in pre-steady state kinetic studies, stopped-flow optical and freeze-quench methods will be used to identify and characterize transient intermediates in the enzyme reaction cycles. Extensive use of site-directed mutagenesis, especially for the toluene/o-xylene system, will enable working hypotheses about specific pathways by which the four substrates access the diiron active sites to be evaluated. The synthesis of accurate biomimetic model compounds will benefit from efficient new designs for preparing dinucleating ligands using macrocycles and dendrimer sheaths as well as from a novel strategy that employs a pendant bridging carboxylate arm. Because of their ability to degrade hydrocarbons, BMMs have been applied for the bioremediation of contaminated seawater, polluted soil environments, and impure drinking water. Their ability to selectively oxidize substrates renders them valuable for synthetic applications in the pharmaceutical and chemical industries. Knowledge of the basic mechanisms of O2 activation and hydrocarbon hydroxylation provided by this research has far-reaching consequences for related non-heme diiron enzymes and will help to establish fundamental principles relating macromolecular structure and function in many other metalloproteins. PUBLIC HEALTH RELEVANCE: By studying both natural systems and synthetic models, this research will reveal how methane-utilizing and related bacteria selectively oxidize hydrocarbons for energy and food by activating oxygen at iron centers housed in their hydroxylase enzymes. The ability of these hydrocarbon-consuming "superbugs" to degrade chlorinated hydrocarbons has led to their application in the bioremediation of industrial wastewater, decontamination of seawater, and removal of soil pollutants.
Funding Period: ----------------1983 - ---------------2014-
more information: NIH RePORT

Top Publications

  1. pmc Dioxygen activation at non-heme diiron centers: oxidation of a proximal residue in the I100W variant of toluene/o-xylene monooxygenase hydroxylase
    Leslie J Murray
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Biochemistry 46:14795-809. 2007
  2. pmc Iron complexes of dendrimer-appended carboxylates for activating dioxygen and oxidizing hydrocarbons
    Min Zhao
    Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    J Am Chem Soc 130:4352-63. 2008
  3. pmc Aging-associated enzyme human clock-1: substrate-mediated reduction of the diiron center for 5-demethoxyubiquinone hydroxylation
    Tsai Te Lu
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Biochemistry 52:2236-44. 2013
  4. pmc A flexible glutamine regulates the catalytic activity of toluene o-xylene monooxygenase
    Alexandria Deliz Liang
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    Biochemistry 53:3585-92. 2014
  5. pmc Evolution of strategies to prepare synthetic mimics of carboxylate-bridged diiron protein active sites
    Loi H Do
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 4307, USA
    J Inorg Biochem 105:1774-85. 2011
  6. pmc A C2-symmetric, basic Fe(III) carboxylate complex derived from a novel triptycene-based chelating carboxylate ligand
    Yang Li
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Dalton Trans 41:9272-5. 2012
  7. pmc Control of substrate access to the active site in methane monooxygenase
    Seung Jae Lee
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 494:380-4. 2013
  8. pmc Non-heme mononitrosyldiiron complexes: importance of iron oxidation state in controlling the nature of the nitrosylated products
    Amit Majumdar
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    Inorg Chem 52:13292-4. 2013
  9. pmc Versatile reactivity of a solvent-coordinated diiron(II) compound: synthesis and dioxygen reactivity of a mixed-valent Fe(II)Fe(III) species
    Amit Majumdar
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    Inorg Chem 53:167-81. 2014
  10. pmc Diiron oxidation state control of substrate access to the active site of soluble methane monooxygenase mediated by the regulatory component
    Weixue Wang
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    J Am Chem Soc 136:2244-7. 2014

Detail Information

Publications52

  1. pmc Dioxygen activation at non-heme diiron centers: oxidation of a proximal residue in the I100W variant of toluene/o-xylene monooxygenase hydroxylase
    Leslie J Murray
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Biochemistry 46:14795-809. 2007
    ..1 and 1.3 V. We also describe the X-ray crystal structure of the I100W variant of ToMOH...
  2. pmc Iron complexes of dendrimer-appended carboxylates for activating dioxygen and oxidizing hydrocarbons
    Min Zhao
    Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    J Am Chem Soc 130:4352-63. 2008
    ..The results are consistent with the formation of a superoxo species. This diiron compound, in the presence of dioxygen, can oxidize external substrates...
  3. pmc Aging-associated enzyme human clock-1: substrate-mediated reduction of the diiron center for 5-demethoxyubiquinone hydroxylation
    Tsai Te Lu
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Biochemistry 52:2236-44. 2013
    ..Both Vmax and kcat/KM for DMQ hydroxylation increase when DMQ0 is replaced by DMQ2 as the substrate, which demonstrates that an isoprenoid side chain enhances enzymatic hydroxylation and improves catalytic efficiency...
  4. pmc A flexible glutamine regulates the catalytic activity of toluene o-xylene monooxygenase
    Alexandria Deliz Liang
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    Biochemistry 53:3585-92. 2014
    ..The role of the pore in the hydroxylase components of other bacterial multicomponent monooxygenases within the superfamily is discussed in light of these conclusions. ..
  5. pmc Evolution of strategies to prepare synthetic mimics of carboxylate-bridged diiron protein active sites
    Loi H Do
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 4307, USA
    J Inorg Biochem 105:1774-85. 2011
    ..The principles and lessons that have emerged from these investigations will guide future efforts to develop more sophisticated diiron protein model complexes...
  6. pmc A C2-symmetric, basic Fe(III) carboxylate complex derived from a novel triptycene-based chelating carboxylate ligand
    Yang Li
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Dalton Trans 41:9272-5. 2012
    ..The (L2(Ph4))(2-) ligand undergoes only minor conformational changes upon formation of the complex...
  7. pmc Control of substrate access to the active site in methane monooxygenase
    Seung Jae Lee
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 494:380-4. 2013
    ..Biological catalysis involving small substrates is often accomplished in nature by large proteins and protein complexes. The structure presented in this work provides an elegant example of this principle...
  8. pmc Non-heme mononitrosyldiiron complexes: importance of iron oxidation state in controlling the nature of the nitrosylated products
    Amit Majumdar
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    Inorg Chem 52:13292-4. 2013
    ..The synthesis, X-ray structures, Mössbauer spectroscopy, cyclic voltammetry, and dioxygen reactivity of [Fe(III)·{FeNO}(7)] are described. ..
  9. pmc Versatile reactivity of a solvent-coordinated diiron(II) compound: synthesis and dioxygen reactivity of a mixed-valent Fe(II)Fe(III) species
    Amit Majumdar
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    Inorg Chem 53:167-81. 2014
    ....
  10. pmc Diiron oxidation state control of substrate access to the active site of soluble methane monooxygenase mediated by the regulatory component
    Weixue Wang
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    J Am Chem Soc 136:2244-7. 2014
    ..The observed conformational change is also consistent with a higher binding affinity of MMOB to MMOH in the diiron(II) state, which may allow MMOB to displace more readily the reductase component (MMOR) from MMOH following reduction. ..
  11. ncbi A planar carboxylate-rich tetraironII complex and its conversion to linear triironII and paddlewheel diironII complexes
    Erwin Reisner
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Inorg Chem 46:10754-70. 2007
    ..The resulting magnetic parameters reveal in most cases weak antiferromagnetic exchange coupling (J typically <3 cm(-1)) and dominant zero-field-splitting parameters...
  12. ncbi Influence of steric hindrance on the core geometry and sulfoxidation chemistry of carboxylate-rich diiron(II) complexes
    Erwin Reisner
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Inorg Chem 46:10229-40. 2007
    ..External thioether substrates were not oxidized when present in oxygenated solutions of paddlewheel and windmill diiron(II) complexes containing 1-methylimidazole or pyridine ligands, respectively...
  13. pmc Desaturase reactions complicate the use of norcarane as a mechanistic probe. Unraveling the mixture of twenty-plus products formed in enzyme-catalyzed oxidations of norcarane
    Martin Newcomb
    Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA
    J Org Chem 72:1121-7. 2007
    ....
  14. pmc X-ray crystal structures of manganese(II)-reconstituted and native toluene/o-xylene monooxygenase hydroxylase reveal rotamer shifts in conserved residues and an enhanced view of the protein interior
    Michael S McCormick
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Am Chem Soc 128:15108-10. 2006
    ..This rotamer shift is conserved between ToMOH and the corresponding residue in methane monooxygenase hydroxylase (MMOH). Previously unidentified hydrophobic pockets similar to those present in MMOH are assigned...
  15. ncbi Water induces a structural conversion and accelerates the oxygenation of carboxylate-bridged non-heme diiron enzyme synthetic analogues
    Min Zhao
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Inorg Chem 45:6323-30. 2006
    ..The presence or absence of water had little effect on the activation enthalpies, suggesting that the loss of water may not be necessary prior to dioxygen binding in the transition state...
  16. pmc Products from enzyme-catalyzed oxidations of norcarenes
    Martin Newcomb
    Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA
    J Org Chem 72:1128-33. 2007
    ..5-15 for the enzymes studied here. The oxidation products found in enzyme-catalyzed oxidations of the norcarenes are useful for understanding the complex product mixtures obtained in norcarane oxidations...
  17. pmc Mechanistic studies of the oxidative N-dealkylation of a substrate tethered to carboxylate-bridged diiron(II) complexes, [Fe2(mu-O2CAr(Tol))2(O2CAr(Tol))2(N,N-Bn2en)2]
    Sungho Yoon
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Inorg Chem 45:5438-46. 2006
    ....
  18. pmc Dioxygen activation at non-heme diiron centers: characterization of intermediates in a mutant form of toluene/o-xylene monooxygenase hydroxylase
    Leslie J Murray
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Am Chem Soc 128:7458-9. 2006
    ..We have tentatively assigned this antiferromagnetically coupled diiron(III) intermediate as a peroxo-bridged cluster, and this complex has also been observed in preliminary studies of the wild-type hydroxylase...
  19. pmc Intermediates in dioxygen activation by methane monooxygenase: a QM/MM study
    David Rinaldo
    Department of Chemistry, Columbia University, New York, New York 10027, USA
    J Am Chem Soc 129:3135-47. 2007
    ..A discrepancy remains in our calculation of the Fe-Fe distance in our model of HQ as compared to EXAFS data obtained several years ago, for which we currently do not have an explanation...
  20. ncbi Synthesis and oxidation of carboxylate-bridged diiron(II) complexes with substrates tethered to primary alkyl amine ligands
    Emily C Carson
    Department of Chemistry, Massachusetts Institute of Technology, Room 18 498, Cambridge, MA 02139, USA
    J Inorg Biochem 100:1109-17. 2006
    ..The six-coordinate iron(III) complex with one bidentate and two monodentate carboxylate ligands, [Fe(O(2)CAr(Xyl))(3)(NH(2)(CH(2))(3)CCH)(2)] (6), was isolated from the reaction mixture following oxidation...
  21. pmc Dioxygen-initiated oxidation of heteroatomic substrates incorporated into ancillary pyridine ligands of carboxylate-rich diiron(II) complexes
    Emily C Carson
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Inorg Chem 45:837-48. 2006
    ..This reaction is sensitive to the choice of carboxylate ligands, however, since the p-tolyl analogue 1 yielded a hexanuclear species, 7, upon oxidation...
  22. pmc Synthesis, characterization, and preliminary oxygenation studies of benzyl- and ethyl-substituted pyridine ligands of carboxylate-rich diiron(II) complexes
    Emily C Carson
    Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Inorg Chem 45:828-36. 2006
    ..Hydrocarbon fragment oxidation occurred for compounds in which the substrate moiety was in close proximity to the diiron center. The extent of oxidation depended upon the exact makeup of the ligand set...
  23. pmc Bifunctional binding of cisplatin to DNA: why does cisplatin form 1,2-intrastrand cross-links with ag but not with GA?
    Yogita Mantri
    Department of Chemistry and School of Informatics, Indiana University, Bloomington, Indiana 47405, USA
    J Am Chem Soc 129:5023-30. 2007
    ..A detailed analysis of the energies and structures of the bifunctional adducts revealed that the observed sugar puckering patterns are necessary for platinum to bind in a relaxed coordination geometry...
  24. pmc Synthesis, structure, and properties of a mixed-valent triiron complex of tetramethyl reductic acid, an ascorbic acid analogue, and its relationship to a functional non-heme iron oxidation catalyst system
    Yoojin Kim
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Inorg Chem 46:6099-107. 2007
    ..In the presence of air and H(2)TMRA, 1 is able to catalyze the oxidation of cyclohexane to cyclohexanol with remarkable selectivity, but the nature of the true catalyst remains unknown...
  25. pmc Characterization of the arene-oxidizing intermediate in ToMOH as a diiron(III) species
    Leslie J Murray
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Am Chem Soc 129:14500-10. 2007
    ....
  26. pmc X-ray structure of a hydroxylase-regulatory protein complex from a hydrocarbon-oxidizing multicomponent monooxygenase, Pseudomonas sp. OX1 phenol hydroxylase
    Matthew H Sazinsky
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Biochemistry 45:15392-404. 2006
    ..Comparisons between the ToMOH and PHH structures provide insights into their substrate regiospecificities...
  27. pmc Tracking a defined route for O₂ migration in a dioxygen-activating diiron enzyme
    Woon Ju Song
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 108:14795-800. 2011
    ..Our findings suggest that other gas-utilizing enzymes may employ similar structural features to effect substrate passage through a protein matrix...
  28. pmc Design and synthesis of a novel triptycene-based ligand for modeling carboxylate-bridged diiron enzyme active sites
    Yang Li
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Org Lett 13:5052-5. 2011
    ..Reaction of L1 with iron(II) triflate and a carboxylate source afforded the desired diiron(II) complex [Fe(2)L1(μ-OH)(μ-O(2)CAr(Tol))(OTf)(2)]...
  29. pmc Analysis of substrate access to active sites in bacterial multicomponent monooxygenase hydroxylases: X-ray crystal structure of xenon-pressurized phenol hydroxylase from Pseudomonas sp. OX1
    Michael S McCormick
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    Biochemistry 50:11058-69. 2011
    ....
  30. pmc Evaluating the identity and diiron core transformations of a (μ-oxo)diiron(III) complex supported by electron-rich tris(pyridyl-2-methyl)amine ligands
    Loi H Do
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    Inorg Chem 51:2393-402. 2012
    ..These findings shed light on the formation of several diiron complexes of electron-rich R(3)TPA ligands and elaborate on conditions required to generate synthetic models of diiron(IV) protein intermediates with this ligand framework...
  31. pmc Current challenges of modeling diiron enzyme active sites for dioxygen activation by biomimetic synthetic complexes
    Simone Friedle
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Chem Soc Rev 39:2768-79. 2010
    ....
  32. pmc Toward functional carboxylate-bridged diiron protein mimics: achieving structural stability and conformational flexibility using a macrocylic ligand framework
    Loi H Do
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Am Chem Soc 133:10568-81. 2011
    ..Compounds 6 and 7 spontaneously convert to a tetrairon(III) complex, [Fe(4)(μ-OH)(6)(PIM)(2)(Ar(Tol)CO(2))(2)] (8), when treated with excess H(2)O...
  33. pmc Mechanistic studies of reactions of peroxodiiron(III) intermediates in T201 variants of toluene/o-xylene monooxygenase hydroxylase
    Woon Ju Song
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Biochemistry 50:5391-9. 2011
    ..Three possible reaction models for the formation and decay of T201(peroxo) were evaluated, and the results demonstrate that this species is on the pathway of arene oxidation and appears to be in equilibrium with ToMOH(peroxo)...
  34. pmc Characterization of a peroxodiiron(III) intermediate in the T201S variant of toluene/o-xylene monooxygenase hydroxylase from Pseudomonas sp. OX1
    Woon Ju Song
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Am Chem Soc 131:6074-5. 2009
    ....
  35. pmc Modeling the syn disposition of nitrogen donors in non-heme diiron enzymes. Synthesis, characterization, and hydrogen peroxide reactivity of diiron(III) complexes with the syn N-donor ligand H2BPG2DEV
    Simone Friedle
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Am Chem Soc 131:14508-20. 2009
    ....
  36. pmc 2-Phenoxypyridyl dinucleating ligands for assembly of diiron(II) complexes: efficient reactivity with O(2) to form (mu-Oxo)diiron(III) units
    Loi H Do
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Inorg Chem 48:10708-19. 2009
    ..The L(Me,Ph) ligand is robust toward oxidative decomposition and does not display any reversible redox activity...
  37. pmc Revisiting the mechanism of dioxygen activation in soluble methane monooxygenase from M. capsulatus (Bath): evidence for a multi-step, proton-dependent reaction pathway
    Christine E Tinberg
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Biochemistry 48:12145-58. 2009
    ..0 and 1.8, respectively, when the reactions are performed in D(2)O. Mechanisms are proposed to account for the observations of these novel intermediates and the proton dependencies of P* to H(peroxo) and H(peroxo) to Q conversion...
  38. pmc Carboxylate as the protonation site in (Peroxo)diiron(III) model complexes of soluble methane monooxygenase and related diiron proteins
    Loi H Do
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Am Chem Soc 132:1273-5. 2010
    ..These results suggest a similar role for protons in the dioxygen activation reactions in soluble methane monooxygenase and related carboxylate-bridged diiron enzymes...
  39. pmc Oxidation reactions performed by soluble methane monooxygenase hydroxylase intermediates H(peroxo) and Q proceed by distinct mechanisms
    Christine E Tinberg
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Biochemistry 49:7902-12. 2010
    ....
  40. pmc Active site threonine facilitates proton transfer during dioxygen activation at the diiron center of toluene/o-xylene monooxygenase hydroxylase
    Woon Ju Song
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Am Chem Soc 132:13582-5. 2010
    ..A mechanism is postulated for dioxygen activation, and possible structures of oxygenated intermediates are discussed...
  41. pmc The aging-associated enzyme CLK-1 is a member of the carboxylate-bridged diiron family of proteins
    Rachel K Behan
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    Biochemistry 49:9679-81. 2010
    ..The direct reaction of NADH with a diiron-containing oxidase enzyme has not previously been encountered for any member of the protein superfamily...
  42. pmc Characterization of iron dinitrosyl species formed in the reaction of nitric oxide with a biological Rieske center
    Christine E Tinberg
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Am Chem Soc 132:18168-76. 2010
    ....
  43. pmc Multiple roles of component proteins in bacterial multicomponent monooxygenases: phenol hydroxylase and toluene/o-xylene monooxygenase from Pseudomonas sp. OX1
    Christine E Tinberg
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    Biochemistry 50:1788-98. 2011
    ..Under these conditions, electron consumption is coupled to H(2)O(2) formation in a hydroxylase-dependent manner. Mechanistic implications of these results are discussed...
  44. pmc Dioxygen activation in soluble methane monooxygenase
    Christine E Tinberg
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, 02139, United States
    Acc Chem Res 44:280-8. 2011
    ..Here our goal is to detail the challenges that we and others face in this research, particularly with respect to some long-standing questions about the system, as well as approaches that might be used to solve them...
  45. pmc Insights into the different dioxygen activation pathways of methane and toluene monooxygenase hydroxylases
    Arteum D Bochevarov
    Department of Chemistry, Columbia University, New York, New York 10027, USA
    J Am Chem Soc 133:7384-97. 2011
    ..Finally, similarities between the oxygen activation mechanisms of the monooxygenases and cytochrome P450 are discussed...
  46. pmc Characterization of a synthetic peroxodiiron(III) protein model complex by nuclear resonance vibrational spectroscopy
    Loi H Do
    Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Chem Commun (Camb) 47:10945-7. 2011
    ..Isotopic (18)O(2) labelling studies revealed a feature involving motion of the {Fe(2)(O(2))}(4+) core that was not previously observed by resonance Raman spectroscopy...