Ribonucleotide reductase structure

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

Thiobacillus ferrooxidans function. 6, 651 Rhus vernicifera stellacyanin structure, 6,651 Riboflavin 5 -phosphate zinc complexes, 5,958 Ribonucleotide reductases cobalt, 6,642 iron, 6,634... 

Sjbberg B-M (1997) Ribonucleotide Reductases - A Group of Enzymes with Different Metallosites and a Similar Reaction Mechanism. 88 139-174 Slebodnick C, Hamstra BJ, Pecoraro VL (1997) Modeling the Biological Chemistry of Vanadium Structural and Reactivity Studies Elucidating Biological Function. 89 51-108 Smit HHA, see Thiel RC (1993) 81 1-40... 

Metalloenzymes with non-heme di-iron centers in which the two irons are bridged by an oxide (or a hydroxide) and carboxylate ligands (glutamate or aspartate) constitute an important class of enzymes. Two of these enzymes, methane monooxygenase (MMO) and ribonucleotide reductase (RNR) have very similar di-iron active sites, located in the subunits MMOH and R2 respectively. Despite their structural similarity, these metal centers catalyze very different chemical reactions. We have studied the enzymatic mechanisms of these enzymes to understand what determines their catalytic activity [24, 25, 39-41]. 

Lassmann, G., Hermann, B., ESR studies of structure and kinetics of radicals from hydroxyurea. An antitumor drug directed against ribonucleotide reductase, Free Radical Biol. Med. 6 (1989), p. 241-244... 

Figure 5. Active site structure of the met form of the E. coli R2 protein of ribonucleotide reductase as determined in a 2.2-A resolution X-ray crystallographic study (14, 102).

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.)...

Kolberg, M., Strand, K.R., Graff, P. and Andersson, K.K. (2004) Structure, function and mechanism of ribonucleotide reductases, Biochim. Biophys. Acta, 1699, 1-34. 

The binuclear iron unit consisting of a (p,-oxo(or hydroxo))bis(p.-carboxylato)diiron core is a potential common structural feature of the active sites of hemerythrin, ribonucleotide reductase, and the purple acid phosphatases. Synthetic complexes having such a binuclear core have recently been prepared their characterization has greatly facilitated the comparison of the active sites of the various proteins. The extent of structural analogy among the different forms of the proteins is discussed in light of their spectroscopic and magnetic properties. It is clear that this binuclear core represents yet another stractural motif with the versatility to participate in different protein functions. 

Nordlund, P., Sj6berg, B.-M., and Eklund, H. (1990). Three-dimensional structure of the free radical protein of ribonucleotide reductase. Nature (London) 345, 593-598. 

A representative sampling of non-heme iron proteins is presented in Fig. 3. Evident from this atlas is the diversity of structural folds exhibited by non-heme iron proteins it may be safely concluded that there is no unique structural motif associated with non-heme iron proteins in general, or even for specific types of non-heme iron centers. Protein folds may be generally classified into several categories (i.e., all a, parallel a/)3, or antiparallel /8) on the basis of the types and interactions of secondary structures (a helix and sheet) present (Richardson, 1981). Non-heme iron proteins are found in all three classes (all a myohemerythrin, ribonucleotide reductase, and photosynthetic reaction center parallel a/)8 iron superoxide dismutase, lactoferrin, and aconitase antiparallel )3 protocatechuate dioxygenase, rubredoxins, and ferredoxins). This structural diversity is another reflection of the wide variety of functional roles exhibited by non-heme iron centers. 

A four-pulse DEER measurement of the distance between two tyrosyl radicals on the monomers that make up the R2 subunit of E. coli ribonucleotide reductase gave a point-dipole distance of 33.1 A, which is in good agreement with the X-ray crystal structure.84 Better agreement between the calculated and observed dipolar frequency could be obtained by summing contributions from distributed... 

In green plants a soluble A9 stearoyl-acyl carrier protein desaturase uses 02 and NADH or NADPH to introduce a double bond into fatty acids. The structure of this protein (Fig. 16-20B,C) is related to those of methane oxygenase and ribonucleotide reductase.333347 Tire desaturase mechanism is discussed in Chapter 21. 

Hydroxyurea interferes with the synthesis of both pyrimidine and purine nucleotides (see table 23.3). It interferes with the synthesis of deoxyribonucleotides by inhibiting ribonucleotide reductase of mammalian cells, an enzyme that is crucial and probably rate-limiting in the biosynthesis of DNA. It probably acts by disrupting the iron-tyrosyl radical structure at the active site of the reductase. Hydroxyurea is in clinical use as an anticancer agent. 

Rather similar ribonucleotide reductases have been isolated from the thermophile, Thermus aquaticus (MW = 80 000) and Anabaena (a blue-green alga) (MW=72 000). The latter enzyme has an absolute requirement for divalent metal cations. The diphosphate reductase from Corynebacterium has a molecular weight of 200 000 and is made up of two subunits. Other enzymes appear to have tetrameric structures.817... 

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