This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. E.coli ribonucleotide reductase catalyzes the conversion of nucleoside diphosphates (NDP) to deoxynucleoside diphosphates. The active protein is composed of two homodimeric subunits (R1 and R2) thought to form a 1:1 complex. R1 binds the NDP substrates, houses the essential cysteines required for catalysis and the binding sites for the allosteric effectors that govern substrate specificity and turnover rates. R2 harbors the essential di-iron tyrosyl radical cofactor on residue 122 (Y?). A major unresolved issue is the mechanism of radical initiation: how the tyrosyl radical (Y?) in R2 generates a transient thiyl radical (C439?) in R1 required for nucleotide reduction. The current model for the radical initiation process involves a specific electron transfer pathway, which traverses a distance of 3.5 nm, derived from a docking model of the R1 and R2 structures, but a substantial part of the pathway is not apparent from the available structural information. A measurement of the distance between Y122 and C439 was imperative to establish the radical initiation model.
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