Ribonucleotide reductase protein

Uhlin, U., Eklund, H. Structure of ribonucleotide reductase protein Rl. Nature 370 553-559, 1994. 

Nordlund, P., and Eklund, H., 1993, Structure and function of the Escherichia coli ribonucleotide reductase protein R2 J. Mol. Biol. 232 1239164. 

Bollinger, J. M., Krehs, C., Vicol, A., Chen, S. X., Ley, B. A., Edmondson, D. E., and Huynh, B. H., 1998, Engineering the diiron site of Escherichia coli ribonucleotide reductase protein R2 to accumulate an intermediate similar to H-peroxo, the putative peroxodiiron(III) complex from the methane monooxygenase catalytic cycle. J. Am. Chem. Soc. 120 1094nl095. 

Climent, L, Sj berg, B.-M., and Huang, C. Y., 1992, Site-directed mutagenesis and deletion of the carboxyl terminus of Escherichia coli ribonucleotide reductase protein R2. Effects on catalytic activity and subunit interaction. Biochemistry 31 4801fi4807. 

Davydov, R., Sahlin, M., Kuprin, S., Gr%oslund, A., and Ehrenberg, A., 1996b, Effect of the tyrosyl radical on the reduction and structure of the Escherichia coli ribonucleotide reductase protein R2 diferric site as probed by EPR on the mixed-valent state. Biochemistry... 

Eriksson, M., Uhlin, U., Ramaswamy, S., Ekberg, M., Regnstr"m, K., Sj"berg, B.-M., and Eklund, H., 1997, Binding of allosteric effectors to ribonucleotide reductase protein Rl reduction of active-site cysteines promotes substrate binding. Structure 5 1077nl092. 

Logan, D. T, deMarE, F., Persson, B. O., Slaby, A., Sj berg, B.-M., and Nordlund, P., 1998, Crystal structures of two self-hydroxylating ribonucleotide reductase protein R2 mutants Structural basis for the oxygen-insertion step of hydroxylation reactions catalyzed by diiron proteins. Biochemistry 37 10798nl0807. 

Lycksell, P.-O., and Sahlin, M., 1995, Demonstration of segmental mobility in the functionally essential carboxyl terminal part of ribonucleotide reductase protein R2 from Escherichia coli. FEBS Lett. 368 441n444. 

Fig. 3. Scheme of various redox states of ribonucleotide reductase protein R2, as well as known reactions to move between the states. Tyr O represents the tyrosyl radical Tyr OH is the normal tyrosyl residue (Y122 in E. coli ribonucleotide reductase),... 

Fig. 2.29 Four-pulse X-band PELDOR of mouse R2 ribonucleotide reductase protein experimental blue line) and simulated red line) spectrum. The modulations are due to the interaction between two tyrosyl radicals at a distance of 3.25 0.05 nm. The figure is reproduced from Ref [58] with permission from the Royal Society of Chemistry...

Svergun et al. [138] studied three proteins lysozyme, Escherichia coli thioredoxin reductase, and E. coli ribonucleotide reductase protein Rl, in aqueous solution, using x-ray and neutron scattering. The density of the water of the first hydiadon shell of these proteins differed from that of bulk water, the average relative deusities were 1.08 0.02, 1.16 0.05, and 1.12 0.06. These experimental values are smaller than those calculated from the packing, 1.22 according to Gerstein and Chothia [137], but still appreciable. 

Uhlin U, Eklund H. 1996. The ten-stranded beta/alpha barrel in ribonucleotide reductase protein Rl. 7Mo/Biol 262 358-369. 

H. 1997. Binding of allosteric effectors to ribonucleotide reductase protein Rl reduction of active-site cysteines promotes substrate binding. Structure 5 1077-1092. 

Kauppi B, Nielsen BA, Ramaswamy S, Larsen IK, Thelander M, Thelander L, Eklund H. 1996. The three-dimensional structure of mammalian ribonucleotide reductase protein R2 reveals a more-accessible iron-radical site than Escherichia coli R2. J Mol Biol 262 706-720. 

Strand KR, Karlsen S, Kolberg M, Rohr AK, Gorbitz CH, Andersson KK. 2004. Crystal structural studies of changes in the native dinnclear iron center of ribonucleotide reductase protein R2 from monse. JBiol Chem 279 46794-46801. 

Figure 1.9 Examples of functionally important intrinsic metal atoms in proteins, (a) The di-iron center of the enzyme ribonucleotide reductase. Two iron atoms form a redox center that produces a free radical in a nearby tyrosine side chain. The iron atoms are bridged by a glutamic acid residue and a negatively charged oxygen atom called a p-oxo bridge. The coordination of the iron atoms is completed by histidine, aspartic acid, and glutamic acid side chains as well as water molecules, (b) The catalytically active zinc atom in the enzyme alcohol dehydrogenase. The zinc atom is coordinated to the protein by one histidine and two cysteine side chains. During catalysis zinc binds an alcohol molecule in a suitable position for hydride transfer to the coenzyme moiety, a nicotinamide, [(a) Adapted from P. Nordlund et al., Nature 345 593-598, 1990.)...

Nordlund, P., Sjoberg, B.-M., Eklund, H. Three-dimensional stmcture of the free radical protein of ribonucleotide reductase. Nature 345 593-598, 1990. 

When induced in macrophages, iNOS produces large amounts of NO which represents a major cytotoxic principle of those cells. Due to its affinity to protein-bound iron, NO can inhibit a number of key enzymes that contain iron in their catalytic centers. These include ribonucleotide reductase (rate-limiting in DNA replication), iron-sulfur cluster-dependent enzymes (complex I and II) involved in mitochondrial electron transport and cis-aconitase in the citric acid cycle. In addition, higher concentrations of NO,... 

Rubrerythrin (Rr) was first isolated in 1988 from cellular extracts of D. vulgaris Hildenborough (38), and later also found in D. desulfuri-cans (39). Rr is constituted by two identical subunits of 22 kDa and it was shown that each monomer contains one Rd-like center, Fe(RS)4, and a diiron-oxo center similar to the ones found in methane monooxygenase (MMO) (40, 41) or ribonucleotide reductase (RNR-R2) (42). After aerobic purification, the UV-visible spectrum shows maxima at 492, 365, and 280 nm, and shoulders at 570 and 350 nm. This spectrum is similar to the ones observed for Rd proteins. From a simple subtraction of a typical Rd UV-vis spectrum (normalized to 492 nm) it is possible to show that the remainder of the spectrum (maxima at 365 nm and a shoulder at 460 nm) strongly resembles the spectrum of met-hemerythrin, another diiron-oxo containing protein. 

The general influence of covalency can be qualitatively explained in a very basic MO scheme. For example, we may consider the p-oxo Fe(III) dimers that are encountered in inorganic complexes and nonheme iron proteins, such as ribonucleotide reductase. In spite of a half-filled crystal-field model), the ferric high-spin ions show quadrupole splittings as large as 2.45 mm s < 0, 5 = 0.53 mm s 4.2-77 K) [61, 62]. This is explained... 

A common way to benefit from the ability to combine different molecular orbital methods in ONIOM is to combine a DFT or ab-initio description of the reactive region with a semi-empirical treatment of the immediate protein environment, including up to 1000 atoms. Due to the requirement for reliable semi-empirical parameters, as discussed in Section 2.2.1, this approach has primarily been used for non-metal or Zn-enzymes. Examples include human stromelysin-1 [83], carboxypeptidase [84], ribonucleotide reductase (substrate reaction) [85], farnesyl transferase [86] and cytosine deaminase [87], Combining two ab-initio methods of different accuracy is not common in biocatalysis applications, and one example from is an ONIOM (MP2 HF) study of catechol O-methyltransferase [88],... 

The application of magnetic resonance techniques to biological systems is a relatively new approach for the study of macromolecules. In this review we have presented the different approaches which have been made to study Bi2-enzymes. Clearly some progress has been made particularly from the application of ESR to a study of the enzymes ethanolamine ammonia-lyase and ribonucleotide reductase. Although 13C NMR is well in its developmental stages it is obvious that this technique will prove to be very useful for the examination of coenzyme-enzyme interactions. Studies of how corrinoids bind in enzymes and how sulfhydryl containing proteins are involved in enzyme catalysis comprise two major problems which must be overcome before realistic mechanisms can be presented for this group of enzymes. 

Un, S., M. Atta et al. (1995). g-values as a probe of the local protein environment High-field EPR of tyrosyl radicals in ribonucleotide reductase and photosystem II. J. Am. Chem. Soc. 117 10713-10719. 

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