Identification of the stable free radical tyrosine residue in ribonucleotide reductase

Abstract

The small subunit of ri~nucIeoside diphosphate reductase contains a unique tyrosine radical and a binuclear iron center. An alignment of different primary structures of the small subunit in Escherichia coli, the marine mollusc Spisula soiidissima, Epstein Barr and Herpes simplex viruses shows that regions comprising residues 115-122, 204-212 and 234-241 (in E.coli numbering) are strikingly similar and are likely to be recognized as functionally important. Two of 16 tyrosine residues and 2 of 8 histidine residues are conserved. We propose that Tyr-122 is responsible for radical stabilization and that His-l 18 and His-241 together with Glu-115 and Asp-237 or Glu-238 are ligands of the iron center.Ribonucleotide reductase Secondary structure prediction Sequence comparison Tyrosine radical

The bacteriophage T4 gene for the small subunit of ribonucleotide reductase contains an intron.

“…From a similar alignment of E. coli B2 with homologues in clam, Epstein-Barr virus and herpes simplex virus a total of 20 conserved residues were found (Sjoberg et al, 1985). These conserved residues include the catalytically essential radical tyrosine residue at position 122 ( Figure 4; Sjoberg et al, 1985;Larsson and Sjoberg, 1986). These conserved residues include the catalytically essential radical tyrosine residue at position 122 ( Figure 4; Sjoberg et al, 1985;Larsson and Sjoberg, 1986).…”

“…The splice junctions indicated in Figure 1 result in a T4 B2 sequence, which is eight residues shorter at the splice point than the corresponding E. coli protein B2 (Figure 4) and the other four nrdB gene products of eukaryotic origins (Sjoberg et al, 1985;Thelander and Berg, 1986). Such a deletion may be tolerated in the B2 protein, since it occurs in an area of rather low homology in the alignment.…”

Analysis of the Protein-Coding Content of the Sequence of Human Cytomegalovirus Strain AD169

“…Mammalian cells contain an iron-tyrosyl radical enzyme, which is the type found in herpes viruses (SJOBERG et al 1985;REICHARD 1989). The enzyme has an O:zfJ2-structure; the HCMV-UL45 gene product is homologous to the o:-(large) RR subunit, and HCMV-UL45 is positionally conserved with the gene for this subunit in other herpesviruses.…”

Spotlight on…Hans Eklund

“…We were the first to solve the structure of the R2 subunit [1], which has interesting free radical chemistry. We observed a di-ion center, close to a tyrosine residue, which stores a free radical [2]. Subsequently, the structure of the R1 subunit was solved [3], and since then we have been working on the R1-R2 complex.…”