Two distinct mechanisms of inactivation of the class Ic ribonucleotide reductase from Chlamydia trachomatis by hydroxyurea: implications for the protein gating of intersubunit electron transfer.

ABSTRACT: Catalysis by a class I ribonucleotide reductase (RNR) begins when a cysteine (C) residue in the alpha(2) subunit is oxidized to a thiyl radical (C(*)) by a cofactor approximately 35 A away in the beta(2) subunit. In a class Ia or Ib RNR, a stable tyrosyl radical (Y(*)) is the C oxidant, whereas a Mn(IV)/Fe(III) cluster serves this function in the class Ic enzyme from Chlamydia trachomatis (Ct). It is thought that, in either case, a chain of Y residues spanning the two subunits mediates C oxidation by forming transient "pathway" Y(*)s in a multistep electron transfer (ET) process that is "gated" by the protein so that it occurs only in the ready holoenzyme complex. The drug hydroxyurea (HU) inactivates both Ia/b and Ic beta(2) subunits by reducing their C oxidants. Reduction of the stable c

SUBMITTER: Jiang W 

PROVIDER: S-EPMC2930177 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature