title: Geometric and electronic structure of the Mn(IV)Fe(III) cofactor in class Ic ribonucleotide reductase: correlation to the class Ia binuclear non-heme iron enzyme.
abstract: The class Ic ribonucleotide reductase (RNR) from Chlamydia trachomatis (Ct) utilizes a Mn/Fe heterobinuclear cofactor, rather than the Fe/Fe cofactor found in the β (R2) subunit of the class Ia enzymes, to react with O2. This reaction produces a stable Mn(IV)Fe(III) cofactor that initiates a radical, which transfers to the adjacent α (R1) subunit and reacts with the substrate. We have studied the Mn(IV)Fe(III) cofactor using nuclear resonance vibrational spectroscopy (NRVS) and absorption (Abs)/circular dichroism (CD)/magnetic CD (MCD)/variable temperature, variable field (VTVH) MCD spectroscopies to obtain detailed insight into its geometric/electronic structure and to correlate structure with reactivity; NRVS focuses on the Fe(III), whereas MCD reflects the spin-allowed transitions mostly on the Mn(IV). We have evaluated 18 systematically varied structures. Comparison of the simulated NRVS spectra to the experimental data shows that the cofactor has one carboxylate bridge, with Mn(IV) at the site proximal to Phe127. Abs/CD/MCD/VTVH MCD data exhibit 12 transitions that are assigned as d-d and oxo and OH(-) to metal charge-transfer (CT) transitions. Assignments are based on MCD/Abs intensity ratios, transition energies, polarizations, and derivative-shaped pseudo-A term CT transitions. Correlating these results with TD-DFT calculations defines the Mn(IV)Fe(III) cofactor as having a μ-oxo, μ-hydroxo core and a terminal hydroxo ligand on the Mn(IV). From DFT calculations, the Mn(IV) at site 1 is necessary to tune the redox potential to a value similar to that of the tyrosine radical in class Ia RNR, and the OH(-) terminal ligand on this Mn(IV) provides a high proton affinity that could gate radical translocation to the α (R1) subunit.
authors.affiliation: Department of Chemistry, Stanford University , Stanford, California 94305, United States.
authors.forename: Yeonju
authors.initials: Y
authors.lastname: Kwak
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Laura M K
authors.initials: LM
authors.lastname: Dassama
authors.forename: Kiyoung
authors.initials: K
authors.lastname: Park
authors.forename: Caleb B
authors.initials: CB
authors.lastname: Bell
authors.forename: Lei V
authors.initials: LV
authors.lastname: Liu
authors.forename: Shaun D
authors.initials: SD
authors.lastname: Wong
authors.forename: Makina
authors.initials: M
authors.lastname: Saito
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Kitao
authors.forename: Makoto
authors.initials: M
authors.lastname: Seto
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yoda
authors.forename: E Ercan
authors.initials: EE
authors.lastname: Alp
authors.forename: Jiyong
authors.initials: J
authors.lastname: Zhao
authors.forename: J Martin
authors.initials: JM
authors.lastname: Bollinger
authors.forename: Carsten
authors.initials: C
authors.lastname: Krebs
authors.forename: Edward I
authors.initials: EI
authors.lastname: Solomon
mesh_terms: D002692:Chlamydia trachomatis / Q000201:enzymology; D018360:Crystallography, X-Ray; D004583:Electrons; D005290:Ferric Compounds / Q000737:chemistry* / Q000378:metabolism; D008345:Manganese / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011789:Quantum Theory; D012264:Ribonucleotide Reductases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; D008345:Manganese; D012264:Ribonucleotide Reductases