Ribonucleotide reductase environment

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],... 

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. 

Fig. 13. Environment of the binuclear iron in ribonucleotide reductase. (Reproduced with permission from Nordlund et al., 1990.)...

CCP provided the first example of a redox-active tryptophan residue in enzyme catalysis (S5), and a second example has just been proposed in ribonucleotide reductase turnover (86). The long half-life of the Trpl91 radical in CCP compound I (ti/2 —3 h) (87), despite the presence of neighboring tyrosine residues (84) which rapidly reduce Trp in aqueous solution (8S), suggests a special radical-stabilizing environ-... 

Giardia, Trichomonas and Entamoeba. These parasitic protozoans differ from the other protozoans discussed in this chapter in that they are all incapable of interconversion between their guanine and adenine nucleotide pools. They are dependent on their host environment to supply them with both guanine and adenine. With the exception of E. histolytica, these parasites lack ribonucleotide reductase. This requires that the host also supply purine and pyrimidine deoxynucleosides. 

The idea of common ancestry of the different ribonucleotide reductases is difficult to test at present because protein sequencing studies have not yet begun. Exchangeability of subunits, possible among the calf thymus and mouse enzymes , has not much been tried. We have seen small but significant stimulation of enzyme activity when the separated, inactive subunits U1 of algal (Scenedesmus) ribonucleotide reductase and B 2 of E. coli were recombined, but not in the reverse combination (B1 -t- U2) . The many individual differences in enzyme structure like Mg or Ca " requirement for subunit interaction, variations in the radical environment as expressed in slightly different ESR spectra (Fig. 3), or details of allosteric effector pattern, do not in principle contradict our reductase model but will in reality severely limit its experimental verification. 

Veselov A, Scholes CP. 1996. X-band ENDOR of the liganding environment from the radical X intermediate of Escherichia coli ribonucleotide reductase. Inorg Chem 35 3702-3705. 

Liu AM, Barra AL, Rubin H, Lu GZ, Graslund A. 2000. Heterogeneity of the local electrostatic environment of the tyrosyl radical in Mycobacterium tuberculosis ribonucleotide reductase observed by high-field electron paramagnetic resonance. J Am Chem Soc 122 1974-1978. 

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