Crystal structure of reduced protein R2 of ribonucleotide reductase: the structural basis for oxygen activation at a dinuclear iron site

Abstract

Carboxylate shifts are often important for carboxylate coordinated metal clusters; they allow the metals to achieve different coordination modes in redox reactions. In the case of reduced R2 these carboxylate shifts allow the formation of accessible reaction sites for dioxygen. The Ser211--> Ala mutant displays a conformational change in the helix containing the mutation, explaining its altered reduction kinetics.

In silico analysis of heme oxygenase structural homologues identifies group‐specific conservations

“…Next, the hydroxyl of Tyr79{179} hydrogen bonds to the side chain carboxylate Glu283{423}, which also interacts with Arg149{268} noted above. The Cα of Thr81{181}, which is fully conserved in all RNRs, is 3.8 Å away from the side chain of Tyr122{227}, which is suggested to be the radical in the enzyme mechanism 19. Lastly, Leu203{327} is involved in hydrophobic packing with the side chain of Gln87{187}, also identified by GEnt.…”

“…Next, Asp84{184} is invariant in all RNRs and coordinates one of the iron ligands 19. The position with the sixth highest Group Entropy score is Glu52{142}, which is on the surface of the molecule near the subunit interface.…”

“…Another residue identified by GEnt that is invariant in all RNRs is Gln87{187}. The OE1 position of Gln87{187} is located 2.9 Å from the side chain carboxylate of Glu204{328}, which is an iron ligand 19. Next, the hydroxyl of Tyr79{179} hydrogen bonds to the side chain carboxylate Glu283{423}, which also interacts with Arg149{268} noted above.…”

“…In the M. trichosporium MMOH alpha chain, Thr213{332} is within 7 Å of the two iron atoms 16. Phe208{332} in RNR1As and Phe162{332} in RNR1Bs form a conserved hydrophobic pocket between the diiron cluster and tyrosyl radical 19, 20.…”

“…Index 183 was identified in RNRs by two of the eight methods performed. The Cβ of Leu83{183} in RNR1A is nearly 6.5 Å from the diiron cluster 19. In hHO1, Ile57{183} is approximately 10 Å from the bound heme 35.…”