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XFEL structure of Class Ib ribonucleotide reductase dimanganese(II) NrdF in complex with hydroquinone NrdI from Bacillus cereusXFEL structure of Class Ib ribonucleotide reductase dimanganese(II) NrdF in complex with hydroquinone NrdI from Bacillus cereus
Structural highlights
FunctionQ81G55_BACCR Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides (By similarity).[PIRNR:PIRNR000355] Publication Abstract from PubMedRedox reactions are central to biochemistry and are both controlled by and induce protein structural changes. Here, we describe structural rearrangements and crosstalk within the Bacillus cereus ribonucleotide reductase R2b-NrdI complex, a di-metal carboxylate-flavoprotein system, as part of the mechanism generating the essential catalytic free radical of the enzyme. Femtosecond crystallography at an X-ray free electron laser was utilized to obtain structures at room temperature in defined redox states without suffering photoreduction. Together with density functional theory calculations, we show that the flavin is under steric strain in the R2b-NrdI protein complex, likely tuning its redox properties to promote superoxide generation. Moreover, a binding site in close vicinity to the expected flavin O2 interaction site is observed to be controlled by the redox state of the flavin and linked to the channel proposed to funnel the produced superoxide species from NrdI to the di-manganese site in protein R2b. These specific features are coupled to further structural changes around the R2b-NrdI interaction surface. The mechanistic implications for the control of reactive oxygen species and radical generation in protein R2b are discussed. Redox-controlled reorganization and flavin strain within the ribonucleotide reductase R2b-NrdI complex monitored by serial femtosecond crystallography.,John J, Aurelius O, Srinivas V, Saura P, Kim IS, Bhowmick A, Simon PS, Dasgupta M, Pham C, Gul S, Sutherlin KD, Aller P, Butryn A, Orville AM, Cheah MH, Owada S, Tono K, Fuller FD, Batyuk A, Brewster AS, Sauter NK, Yachandra VK, Yano J, Kaila VRI, Kern J, Lebrette H, Hogbom M Elife. 2022 Sep 9;11. pii: 79226. doi: 10.7554/eLife.79226. PMID:36083619[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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