Nikas, I., McLauchlan, J., Davison, A.J., Taylor, W.R., and Clements, J.B. (1986) Structural features of ribonucleotide reductase. Proteins: Structure Function and Bioinformatics, 1(4), pp. 376-84. (doi:10.1002/prot.340010411)
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Herpes simplex virus type 1 (HSV-1) encodes a ribonucleotide reductase which comprises two polypeptides with sizes of 136,000 (RR1) and 38,000 mol. wt. (RR2). We have determined the entire DNA sequence specifying HSV-1 RR1 and have identified two adjacent open reading frames in varicella-zoster virus (VZV) which have homology to HSV RR1 and RR2; the predicted sizes for the VZV RR1 and RR2 polypeptides are 87,000 and 35,000 mol. wt. respectively. Amino acid comparisons with RR1 and RR2 polypeptides from other organisms indicate that HSV-1 RR1 contains a unique N-terminal domain which is absent from other RR1 polypeptides apart from HSV-2 RR1. These N-terminal amino acid sequences are poorly conserved between HSV-1 and HSV-2 in contrast to the remainder of the protein which shows greater than 90% homology. Polypeptide structural predictions suggest that the HSV-1 N-terminal domain may be separated into two regions, namely, a beta-sheet structure followed by a nonstructured area. Across the remainder of RR1 and RR2, comparisons also reveal blocks of amino acids conserved between the different ribonucleotide reductases, and these may be important for enzyme activity. From predictions on the structure of these conserved blocks, we have proposed that the location of a substrate binding site within RR1 is centered on three conserved glycine residues in a region which is predicted to adopt a beta-sheet/turn/alpha-helical structure; this approximates to the structure for ADP nucleotide binding folds. Finally, we propose that the promoters for the HSV and Epstein-Barr virus (EBV) RR2 transcripts have evolved by separate evolutionary routes.
|Glasgow Author(s) Enlighten ID:||Davison, Dr Andrew and McLauchlan, Dr John|
|Authors:||Nikas, I., McLauchlan, J., Davison, A.J., Taylor, W.R., and Clements, J.B.|
|College/School:||College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation|
|Journal Name:||Proteins: Structure Function and Bioinformatics|
|Published Online:||3 February 2004|
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