Ribonucleotide reductase radical transfer pathway

Abbreviations AdoCbl, deoxyadenosylcobalamin AdoMet, S-adenosyl methionine dopa, 3,4-dihydroxyphenylalanine ENDOR, electron nuclear double resonance EPR, electron paramagnetic resonance NMR, nuclear magnetic resonance RNR, ribonucleotide reductase RTF, radical transfer pathway. 

Rova, U., Adrait, A., PTsch, S., Gr%oslund, A., and Thelander, L., 1999, Evidence by mutagenesis that Tyr(370) of the mouse ribonucleotide reductase R2 protein is the connecting link in the intersubunit radical transfer pathway. J. Biol. Chem. 274 23746n23751. 

Schmidt, P. P., Rova, U., Katterle, B., Thelander, L., and Gr%oslund, A., 1998, Kinetic evidence that a radical transfer pathway in protein R2 of mouse ribonucleotide reductase is involved in generation of die tyrosyl free radical. J. Biol. Chem. 273 21463n21472. 

Graslund A. 2002. Ribonucleotide reductase Kinetic methods for demonstrating radical transfer pathway in protein R2 of mouse enzyme in generation of tyrosyl free radical. In Enzyme kinetics and mechanism, Pt F detection and characterization of enzyme reaction intermediates, pp. 399 14. New York Academic Press. 

A chain of hydrogen-bonded side chains apparently provides a pathway for transfer of an impaired electron from the active site to the Tyr 122 radical and from there to the radical generating center.363 The tyrosyl radical can be destroyed by removal of the iron by exposure to 02 or by treatment of ribonucleotide reductases with hydroxyurea, which reduces the radical and also destroys catalytic activity ... 

Figure 16-21 (A) Scheme showing the diiron center of the R2 subunit of E. coli ribonucleotide reductase. Included are the side chains of tyrosine 122, which loses an electron to form a radical, and of histidine 118, aspartate 237, and tryptophan 48. These side chains provide a pathway for radical transfer to the R1 subunit where the chain continues to tyrosines 738 and 737 and cysteine 429.354a c From Andersson et al.35ic (B) Schematic drawing of the active site region of the E. coli class IH ribonucleotide reductase with a plausible position for a model-built substrate molecule. Redrawn from Lenz and Giese373 with permission.

In Ribonucleotide reductase, finally, the radical transfer mechanism between the stable tyrosyl radical in the R2 subunit and the cysteine residue at the R1 active site is outlined, and shown to primarily invoke a neutral H-atom transfer pathway, with very low barriers and thermoneutrality. In addition, the substrate mechanism is outlined, based again on a model slightly modified compared with the original experimental proposals. 

Fig. 4. Suggested long-range electron transfer pathway from the substrate binding site in protein R1 to the tyrosyl radical in protein R2 in E. coli ribonucleotide reductase. The figure is adapted from (73) with permission from B-M. Sjoberg.

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