Escherichia coli and herpes-simplex-virus ribonucleotide reductase R2 subunit. Compared reactivities of the redox centres.
Protein R2, the small subunit of ribonucleotide reductase, contains a diferric centre and a tyrosyl radical absolutely required for enzyme activity. The reduction of the tyrosyl radical and the mobilization of the iron centre result in the inhibition of the enzyme and thus of DNA synthesis. The chemical reactivity of the iron-radical centre of Escherichia coli and herpes simplex virus has been studied by u.v.-visible and e.p.r. spectroscopies. The tyrosyl radical is efficiently scavenged by hydroxamic acids and phenols during reactions controlled by steric hindrance and hydrophobic interactions. The reaction with o-disubstituted phenols yields the corresponding diphenoquinones. The reactivity of the bacterial radical greatly contrasts with that of the viral radical, and the iron centre in herpes-simplex-virus R2 is much more labile than that in E. coli R2, as shown from the facile mobilization of iron by chelators such as catechol. These results suggest that the active sites of the two enzymes are significantly different and might be useful for designing new antiviral agents.
Laboratoire d'Etudes Dynamiques et Structurales de la Sélectivité, Université Joseph Fourier, Grenoble, France.
M
M
Atta
N
N
Lamarche
J P
JP
Battioni
B
B
Massie
Y
Y
Langelier
D
D
Mansuy
M
M
Fontecave
D001665:Binding Sites; D002396:Catechols / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004926:Escherichia coli / Q000201:enzymology*; D016166:Free Radical Scavengers; D005609:Free Radicals; D006877:Hydroxamic Acids / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D010084:Oxidation-Reduction; D010636:Phenols / Q000378:metabolism; D011809:Quinones / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000737:chemistry / Q000378:metabolism*; D018139:Simplexvirus / Q000201:enzymology*; D013056:Spectrophotometry, Ultraviolet; D014443:Tyrosine / Q000378:metabolism
D002396:Catechols; D016166:Free Radical Scavengers; D005609:Free Radicals; D006877:Hydroxamic Acids; D010636:Phenols; D011809:Quinones; D014443:Tyrosine; D007501:Iron; D012264:Ribonucleotide Reductases; C034221:catechol