| Attributs | Valeurs |
|---|
| type
| |
| Is Part Of
| |
| Subject
| |
| Title
| - The Crystal Structure of an Azide Complex of the Diferrous R2Subunit of Ribonucleotide Reductase Displays a Novel CarboxylateShift with Important Mechanistic Implications for Diiron-CatalyzedOxygen Activation
|
| has manifestation of work
| |
| related by
| |
| Author
| |
| Abstract
| - The dinuclear Fe-center in the R2 protein of ribonucleotide reductase catalyzes oxygen activationchemistry leading to generation of the essential stable tyrosyl radical. Related oxygen reactions occur in severalother diiron-containing enzyme systems where highly oxidative reaction intermediates are required to activatethe substrates. Two such examples are methane monooxygenase and Δ9 stearoyl-acyl carrier protein desaturasewhere oxygen activation takes place at Fe-centers whose structures are similar to the Fe-center in R2. In anattempt to structurally characterize the nature of the dioxygen cleavage reaction performed by these proteinswe have determined the crystal structures of two different forms of the diferrous R2 protein in the presenceof azide, a potential Fe ligand. In crystals of the wt protein no azide binding was detected. The mutant proteinF208A/Y122F has a larger hydrophobic pocket around the Fe-center and in the structure of this protein azidebind as an η1-terminal ligand to Fe2, the Fe ion farthest away from the tyrosine residue to be oxidized in theradical generation reaction. Glu 238, the Fe ligand most exposed into the hydrophobic pocket, coordinates theFe-center in a novel μ-(η2,η1) bridging mode with one of the carboxylate oxygen atoms forming a bridgebetween the two iron ions and the other oxygen being coordinated to Fe2. Through this bridging the Fe−Fedistance is shortened to about 3.4 Å as compared to 3.9 Å for the structure of the reduced wt protein. On thebasis of the novel carboxylate shift and recent data on the spectroscopic properties of the key intermediate Xwe propose a unique structure for intermediate X and a detailed mechanism for dioxygen cleavage. Thismechanism suggests an asymmetric oxygen cleavage with a terminal oxo/hydroxo group as the major speciesresponsible for substrate activation.
|
| article type
| |
| is part of this journal
| |
