The critical C-terminus of the small subunit of herpes simplex virus ribonucleotide reductase is mobile and conformationally similar to C-terminal peptides

The C-terminus of the small subunit of class I ribonucleotide reductases is essential for subunit association and enzymatic activity. ¹H NMR analysis of the small subunit (2 × 38 kDa as a homodimer) of herpes simplex virus ribonucleotide reductase shows that this critical binding site is mobile and exposed in relation to the rest of the protein. Assignments of six C-terminal amino acids are made by comparing the TOCSY and NOESY spectra of the small subunit with the spectra of an identical protein truncated by seven amino acids at the C-terminus and the spectra of an analogous 15 amino acid peptide. The mobility of the C-terminus may be important for subunit recognition and could be general for other ribonucleotide reductases. The spectral comparisons also suggest that the six C-terminal amino acids of the small subunit and peptide are confor-mationally similar. This observation may be important for the design of inhibitors of ribonucleotide reductase subunit association. © Munksgaard 1994.