6i94

R2-like ligand-binding oxidase G68L mutant with non-activated Mn/Mn cofactor (after aerobic reconstitution with Mn and Fe)

spinqualitylabelsall models 6i94, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6i94 is a 1 chain structure with sequence from Geobacillus kaustophilus HTA426. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.703Å Ligands: MN, OCA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q5KW80_GEOKA Publication Abstract from PubMed A heterobimetallic Mn/Fe cofactor is present in the R2 subunit of class Ic ribonucleotide reductases (R2c) and in R2-like ligand-binding oxidases (R2lox). Although the protein-derived metal ligands are the same in both groups of proteins, the connectivity of the two metal ions and the chemistry each cofactor performs are different: in R2c, a one-electron oxidant, the Mn/Fe dimer is linked by two oxygen bridges (mu-oxo/mu-hydroxo), whereas in R2lox, a two-electron oxidant, it is linked by a single oxygen bridge (mu-hydroxo) and a fatty acid ligand. Here, we identified a second coordination sphere residue that directs the divergent reactivity of the protein scaffold. We found that the residue that directly precedes the N-terminal carboxylate metal ligand is conserved as a glycine within the R2lox group, but not in R2c. Substitution of the glycine with leucine converted the resting-state R2lox cofactor to an R2c-like cofactor, a micro-oxo/micro-hydroxo-bridged MnIII/FeIII dimer. This species has recently been observed as an intermediate of the oxygen activation reaction in wild-type R2lox, indicating that it is physiologically relevant. Cofactor maturation in R2c and R2lox therefore follows the same pathway, with structural and functional divergence of the two cofactor forms following oxygen activation. We also show that the leucine-substituted variant no longer functions as a two-electron oxidant. Our results reveal that the residue preceding the N-terminal metal ligand directs the cofactor's reactivity toward one- or two-electron redox chemistry, presumably by setting the protonation state of the bridging oxygens and thereby perturbing the redox potential of the Mn ion. Chemical flexibility of heterobimetallic Mn/Fe cofactors: R2lox and R2c proteins.,Kutin Y, Kositzki R, Branca RMM, Srinivas V, Lundin D, Haumann M, Hogbom M, Cox N, Griese JJ J Biol Chem. 2019 Oct 7. pii: RA119.010570. doi: 10.1074/jbc.RA119.010570. PMID:31591267 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribonucleotide reductase 3D structures

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