Methane monooxygenase hydroxylase

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.)...

Proteins with dinuclear iron centres comprise some well studied representatives like ribonucleotide reductase (RNR), purple acid phosphatase (PAP), methane monooxygenase hydroxylase (MMOH), ruberythrin and hemerythrin. The latter is an oxygen carrier in some sea worms it has been first characterized within this group and has thus laid the foundation to this class of iron coordination motif. Ruberythrin is found in anaerobic sulfate-reducing bacteria. Its name implies that, in addition to a hemerythrin-related diiron site another iron is coordinated in a mononuclear fashion relating to rubredoxin which is an iron-... 

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.

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-... 

Willems, J-P., Valentine, A.M., Gurbiel, R., Lippard, S.J., and Hoffman, B.M. (1998) Small molecule binding to the mixed-valent diiron center of methane monooxygenase hydroxylase from Methylococcus capsulatus... 

Andersson, K. K., Eroland, W. A., Lee, S.-K., and Lipscomb, J. D., 1991, Dioxygen independent oxygenation of hydrocarbons by methane monooxygenase hydroxylase component. New J. Chem. 15 411n415. 

Fox, B. G., and Lipscomb, J. D., 1988, Purification of a high specific activity methane monooxygenase hydroxylase component from a type II methanotroph, Biochem. Biophys. Res. Commun. 154 165nl70. 

Kim, K., and Lippard, S. J., 1996, Structure and M ssbauer spectrum of a (p-l,2-peroxo)-bis( r-carboxylato)diiron(III) model for the peroxo intermediate in the methane monooxygenase hydroxylase reaction cycle, J. Am. Chem. Soc. 118 4914n4915. 

Rosenzweig, A. C., Brandstetter, H., Whittington, D. A., Wordlund, P., Lippard, S. J., and Frederick, C. A., 1997, Crystal structures of the methane monooxygenase hydroxylase from Methylococcus capstdatus (Bath) implications for substrate gating and component interactions. Proteins 29 1419152. 

Shu, L., Liu,Y., Lipscomb, J. D., and Que, L., Jr., 1996, EXAFS studies of the methane monooxygenase hydroxylase component from Methylosinus trichosporium OB3b, JBIC l 297n304. 

Scheme 2 Reaction cycle for methane monooxygenase hydroxylase...

Fig. 2. Diferric iron clusters from ribonucleotide reductase R2 subunit and methane monooxygenase hydroxylase. The drawings are based on (18, 19) for RNR-R2 and (15) for MMOH.

Fig. 1. Diferric iron clusters form hemer3fthrin, ribonucleotide reductase R2 subunit, and methane monooxygenase hydroxylase. The figure was made with the RasMol 2.0 program, and the protein coordinates as PDB files were obtained from Brookhaven Protein Data Bank. Only the amino acids (histidines, green carboxylates, black oxygen, red nitrogen, yellow acetate, blue iron, violet) coordinated to the iron cluster are shown, coordinated waters are not indicated. The first subunit containing the cluster is shown. Diferric Hr is from sipunculid worm Themiste dyscritra). The RNR-R2 is from E. coli. The MMOH is from Methvlococcus caosulatus (Bath).

FIGURE 4.35 Mechanistic scheme for substrate hydroxylation catalyzed by soluble methane monooxygenase (hydroxylase component) (sMMOH).17,76... 

Lee, S.-K. and J.D. Lipscomb (1999). Oxygen activation catalyzed by methane monooxygenase hydroxylase component Proton delivery during the 0-0 bond cleavage steps. Biochemistry 38, 4423-4432. 

Figure 15-4 Schematic diagrams comprising dinuclear metal centers in HuHF, EcFtna and EcBfr with those of ribonucleotide reductase R2 subunit (RNR R2), methane monooxygenase hydroxylase component (MMOH) and DvRr. The third metal sites in HuHF and EcFtna are also indicated.

M. T. Stankovich, K. E. Paulsen, Y. Liu, and J. D. Lipscomb. Redox properties of methane monooxygenase hydroxylase and regulation by component B. Abstracts of the 205th ACS Meeting, INOR566, (1993). 

We will compare some aspects of the reaction pathway and properties of the O2 carrier protein hemerythrin (Hr) with the early parts of the reaction cycles of the structurally related enzymes methane monooxygenase hydroxylase (MMOH) and ribonucleotide reductase (RNR). A general structural comparison of these three proteins is given in Figure 4 for the diferric and diferrous... 

MacArthur R, Sazinsky MH, Kuhne H, Whittington DA, Lippard SJ, Brudvig GW. 2002. Component B binding to the soluble methane monooxygenase hydroxylase by saturation-recovery EPR spectroscopy of spin-labeled MMOB. J Am Chem Soc 124(45) 13392-13393. 

Andersson KK, Froland WA, Lee SK, Lipscomb JD. 1991. Dioxygen independent oxygenation of hydrocarbons by methane monooxygenase hydroxylase component. 

Liu Y, Nesheim JC, Lee S-K, Lipscomb JD. 1995. Gating effects of component b on oxygen activation by the methane monooxygenase hydroxylase component. J Biol Chem 270 24662-24665. 

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