Structural basis on the dityrosyl-diiron radical cluster and the functional differences of human ribonucleotide reductase small subunits hp53R2 and hRRM2.

ABSTRACT: Ribonucleotide reductase (RNR) is an enzyme for the de novo conversion of ribonucleotides to deoxyribonucleotides. The two human RNR small subunits hRRM2 and hp53R2 share 83% sequence homology but show distinct expression patterns and function. Structural analyses of the oxidized form of hRRM2 and hp53R2 indicate that both proteins contain a conserved Gln127-hp53R2/Gln165-hRRM2 close to the dinuclear iron center and the essential tyrosine residue Tyr124-hp53R2/Tyr162-hRRM2 forms hydrogen bonds with the tyrosine and iron ligands, implying a critical role for the glutamine residue in assembling the dityrosyl-diiron radical cofactor. The present work also showed that Tyr221 in hRRM2, which is replaced by Phe183 in hp53R2, forms a hydrogen bond with Tyr162 to extend the hydrogen bond network f

SUBMITTER: Zhou B 

PROVIDER: S-EPMC3050530 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature