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Crystal structures of two self-hydroxylating ribonucleotide reductase protein R2 mutants : Structural basis for the oxygen-insertion step of hydroxylation reactions catalyzed by diiron proteins

Logan, Derek T. LU orcid ; deMaré, Fredrick ; Persson, Bert O. ; Slaby, Agneta ; Sjöberg, Britt Marie and Nordlund, Pär (1998) In Biochemistry 37(30). p.10798-10807
Abstract

The R2 protein of ribonucleotide reductase catalyzes the dioxygen- dependent one-electron oxidation of Tyr122 at a diiron-carboxylate site. Methane monooxygenase and related hydroxylases catalyze hydrocarbon hydroxylation at diiron sites structurally related to the one in R2. In protein R2, the likely reaction site for dioxygen is close to Phe208. The crystal structure of an iron ligand mutant R2, Y122F/E238A, reveals the hydroxylation of Phe208 at the meta, or ε-, ring position and the subsequent coordination of this residue to the diiron site. In another mutant, F208Y, the 'foreign' residue Tyr208 is hydroxylated to Dopa. The structures of apo and diferrous F208Y presented here suggest that Tyr208 is coordinated to the iron site of... (More)

The R2 protein of ribonucleotide reductase catalyzes the dioxygen- dependent one-electron oxidation of Tyr122 at a diiron-carboxylate site. Methane monooxygenase and related hydroxylases catalyze hydrocarbon hydroxylation at diiron sites structurally related to the one in R2. In protein R2, the likely reaction site for dioxygen is close to Phe208. The crystal structure of an iron ligand mutant R2, Y122F/E238A, reveals the hydroxylation of Phe208 at the meta, or ε-, ring position and the subsequent coordination of this residue to the diiron site. In another mutant, F208Y, the 'foreign' residue Tyr208 is hydroxylated to Dopa. The structures of apo and diferrous F208Y presented here suggest that Tyr208 is coordinated to the iron site of F208Y throughout the Dopa generation cycle. Together, the structural data on these two mutants suggest two possible reaction geometries for the hydroxylation reaction catalyzed by these modified R2 diiron sites, geometries which might be relevant for the hydroxylation reaction catalyzed by other diiron sites such as methane monooxygenase. A critical role for residue Glu238 in directing the oxidative power of the reactive intermediate toward oxidation of Tyr122 is proposed.

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type
Contribution to journal
publication status
published
subject
in
Biochemistry
volume
37
issue
30
pages
10 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • scopus:0032575296
  • pmid:9692970
ISSN
0006-2960
DOI
10.1021/bi9806403
language
English
LU publication?
no
id
20bbe35d-263c-43e8-b531-78595e893273
date added to LUP
2022-04-25 11:25:30
date last changed
2024-02-17 23:12:45
@article{20bbe35d-263c-43e8-b531-78595e893273,
  abstract     = {{<p>The R2 protein of ribonucleotide reductase catalyzes the dioxygen- dependent one-electron oxidation of Tyr122 at a diiron-carboxylate site. Methane monooxygenase and related hydroxylases catalyze hydrocarbon hydroxylation at diiron sites structurally related to the one in R2. In protein R2, the likely reaction site for dioxygen is close to Phe208. The crystal structure of an iron ligand mutant R2, Y122F/E238A, reveals the hydroxylation of Phe208 at the meta, or ε-, ring position and the subsequent coordination of this residue to the diiron site. In another mutant, F208Y, the 'foreign' residue Tyr208 is hydroxylated to Dopa. The structures of apo and diferrous F208Y presented here suggest that Tyr208 is coordinated to the iron site of F208Y throughout the Dopa generation cycle. Together, the structural data on these two mutants suggest two possible reaction geometries for the hydroxylation reaction catalyzed by these modified R2 diiron sites, geometries which might be relevant for the hydroxylation reaction catalyzed by other diiron sites such as methane monooxygenase. A critical role for residue Glu238 in directing the oxidative power of the reactive intermediate toward oxidation of Tyr122 is proposed.</p>}},
  author       = {{Logan, Derek T. and deMaré, Fredrick and Persson, Bert O. and Slaby, Agneta and Sjöberg, Britt Marie and Nordlund, Pär}},
  issn         = {{0006-2960}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{30}},
  pages        = {{10798--10807}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Biochemistry}},
  title        = {{Crystal structures of two self-hydroxylating ribonucleotide reductase protein R2 mutants : Structural basis for the oxygen-insertion step of hydroxylation reactions catalyzed by diiron proteins}},
  url          = {{http://dx.doi.org/10.1021/bi9806403}},
  doi          = {{10.1021/bi9806403}},
  volume       = {{37}},
  year         = {{1998}},
}