title: Formation and function of the Manganese(IV)/Iron(III) cofactor in Chlamydia trachomatis ribonucleotide reductase.
abstract: The beta(2) subunit of a class Ia or Ib ribonucleotide reductase (RNR) is activated when its carboxylate-bridged Fe(2)(II/II) cluster reacts with O(2) to oxidize a nearby tyrosine (Y) residue to a stable radical (Y(*)). During turnover, the Y(*) in beta(2) is thought to reversibly oxidize a cysteine (C) in the alpha(2) subunit to a thiyl radical (C(*)) by a long-distance ( approximately 35 A) proton-coupled electron-transfer (PCET) step. The C(*) in alpha(2) then initiates reduction of the 2' position of the ribonucleoside 5'-diphosphate substrate by abstracting the hydrogen atom from C3'. The class I RNR from Chlamydia trachomatis (Ct) is the prototype of a newly recognized subclass (Ic), which is characterized by the presence of a phenylalanine (F) residue at the site of beta(2) where the essential radical-harboring Y is normally found. We recently demonstrated that Ct RNR employs a heterobinuclear Mn(IV)/Fe(III) cluster for radical initiation. In essence, the Mn(IV) ion of the cluster functionally replaces the Y(*) of the conventional class I RNR. The Ct beta(2) protein also autoactivates by reaction of its reduced (Mn(II)/Fe(II)) metal cluster with O(2). In this reaction, an unprecedented Mn(IV)/Fe(IV) intermediate accumulates almost stoichiometrically and decays by one-electron reduction of the Fe(IV) site. This reduction is mediated by the near-surface residue, Y222, a residue with no functional counterpart in the well-studied conventional class I RNRs. In this review, we recount the discovery of the novel Mn/Fe redox cofactor in Ct RNR and summarize our current understanding of how it assembles and initiates nucleotide reduction.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. wuj101@psu.edu
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Danny
authors.initials: D
authors.lastname: Yun
authors.forename: Lana
authors.initials: L
authors.lastname: Saleh
authors.forename: J Martin
authors.initials: JM
authors.lastname: Bollinger
authors.forename: Carsten
authors.initials: C
authors.lastname: Krebs
mesh_terms: D002384:Catalysis; D002692:Chlamydia trachomatis / Q000201:enzymology*; D003067:Coenzymes / Q000737:chemistry*; D007501:Iron; D008345:Manganese; D010084:Oxidation-Reduction; D012264:Ribonucleotide Reductases / Q000737:chemistry*
chemical_list: D003067:Coenzymes; D008345:Manganese; D007501:Iron; D012264:Ribonucleotide Reductases