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 x 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 conformationally similar. This observation may be important for the design of inhibitors of ribonucleotide reductase subunit association.
Laplante
S R
SR
Bio-Méga/Boehringer Ingelheim Research Inc., Laval, Québec, Canada.
Aubry
N
N
Liuzzi
M
M
Thelander
L
L
Ingemarson
R
R
Moss
N
N
D001665:Binding Sites; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D012264:Ribonucleotide Reductases / Q000737:chemistry*; D018139:Simplexvirus / Q000201:enzymology*
D010455:Peptides; D012264:Ribonucleotide Reductases