Structural Basis for Superoxide Activation of Flavobacterium johnsoniae Class I Ribonucleotide Reductase and for Radical Initiation by Its Dimanganese Cofactor
Year: 2018
Type: article
Abstract: A ribonucleotide reductase (RNR) from Flavobacterium johnsoniae ( Fj ) differs fundamentally from known (subclass a–c) class I RNRs, warranting its assignment to a new subclass, Id. Its β subunit shares with Ib counterparts the requirements for manganese(II) and superoxide (O 2 – ) for activation, but it does not require the O 2 – -supplying flavoprotein (NrdI) needed in Ib systems, instead scavenging the oxidant from solution. Although Fj β has tyrosine at the appropriate sequence position (Tyr 104), this residue is not oxidized to a radical upon activation, as occurs in the Ia/b proteins. Rather, Fj β directly deploys an oxidized dimanganese cofactor for radical initiation. In treatment with one-electron reductants, the cofactor can undergo cooperative three-electron reduction to the II/II state, in contrast to the quantitative univalent reduction to inactive “met” (III/III) forms seen with I(a–c) βs. This tendency makes Fj β unusually robust, as the II/II form can readily be reactivated. The structure of the protein rationalizes its distinctive traits. A distortion in a core helix of the ferritin-like architecture renders the active site unusually open, introduces a cavity near the cofactor, and positions a subclass-d-specific Lys residue to shepherd O 2 – to the Mn 2 II/II cluster. Relative to the positions of the radical tyrosines in the Ia/b proteins, the unreactive Tyr 104 of Fj β is held away from the cofactor by a hydrogen bond with a subclass-d-specific Thr residue. Structural comparisons, considered with its uniquely simple mode of activation, suggest that the Id protein might most closely resemble the primordial RNR-β.
Source: Biochemistry
Language: English
Subfield: Inorganic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Funders: Howard Hughes Medical Institute, U.S. Department of Energy, Massachusetts Institute of Technology, Searle Scholars Program, National Institutes of Health, Office of Science, Michigan Technology Tri-Corridor, National Cancer Institute, National Institute of General Medical Sciences, Basic Energy Sciences, Office of Research Infrastructure Programs, National Institutes of Health, Argonne National Laboratory, SLAC National Accelerator Laboratory
Awards: G102163711, G107546177, G1229526393, G1286236842, G1286251239, G1313983767, G1451874870, G1664757510, G170736304, G1947107004, G2287611682, G2371548206, G2539837713, G262532246, G262962599, G2638771445, Functional diversification of the HD-superfamily; the Hydrolase/Oxygenase Dilemma, G2709439402, Mechanisms of Radical Translocation in Class I Ribonucleotide Reductases, G303061748, G30714459, G3075337988, G3083819904, G3127483976, G3152346458, G3329398301, G3525367178, G382641700, Mechanistic Determination of the Non-heme Iron Enzyme Hyoscyamine-6-hydroxylase, G3887162018, High-Speed High-Sensitivity Detector for X-ray Micro-Crystallography at GM/CA@APS, G3913106684, G409777406, G416541740, G419881185, G4235786860, G426311843, G4269941704, G42916606, G4356617607, G4501827968, G4581610328, G469876061, G4773269573, G495301720, G498139845, G5082572234, G5356207468, G5387317844, G5570207115, G5607048534, G5906309288, G6072549038, G618388848, G650090426, G6550344761, G6767173602, G6848031779, G6918803902, G7147508703, G7283024673, G735966847, G7583137537, Structure determination of reaction intermediates in macromolecular complexes, Structure determination of reaction intermediates in macromolecular complexes, Functional diversification of the HD-superfamily; the Hydrolase/Oxygenase Dilemma, G8382000481, G8473838722, G8925327636, G8927075130, G9000014584, G9000019894, G9000088142, Mapping the structural basis for mechanistic diversity in metalloenzyme superfamilies, G911061179, G969889393, G993149817
OpenAlex ID: W2796366830