FeSuperoxide Dismutase

Abstract

Iron‐containing superoxide dismutases (FeSOD) are generally dimers of identical 21‐kDa monomers, each of which contains a single active site. Each active site binds one Fe ion with roughly trigonal bipyramidal geometry, employing two His and an Asp − residue as equatorial ligands, and one more His and a coordinated solvent as axial ligands. In the course of the catalytic cycle, the Fe alternates between the +3 and +2 states, and the coordinated solvent is believed to alternate between OH − and H 2 O, in concert. Activity is inhibited by coordination of F − , N 3 − , or OH − to the oxidized state. Decreased activity at high pH reflects the latter in addition to ionization of the conserved Tyr34 in the reduced state of the enzyme at pH 8.5. Despite strong structural homologies with the manganese containing superoxide dismutases (MnSODs), many FeSODs are inactive when reconstituted with Mn, and in the case of Escherichia coli SODs this appears to reflect, at least in part, very large differences in the reduction potentials produced by the two different SOD proteins, either Fe or Mn. Subtle changes in strengths of key active site H‐bonds could differently tune the p K s of the coordinated solvent molecule, whose participation in proton‐coupled electron transfer would in turn cause these differences to contribute to different reduction potentials, in the two proteins. Thus, SOD suggests that H‐bond mediated tuning of the protonation state and p K s of redox‐coupled coordinated solvents may serve as a means of tuning the E m in other cases as well.

Structural basis for nitrous oxide generation by bacterial nitric oxide reductases

“…Another possible structural change in the binuclear centre of NOR in the catalytic turnover would be dissociation of one of the ligands (His258, His259 or Glu211) from Fe B , thus opening space for accommodation of a second NO molecule in the binuclear centre. Non-haem irons having two His and one Glu/Asp ligands are generally observed in nature, in which one of the coordination sites is occupied by a water molecule [55][56][57]. In addition, in the crystal structure of quercetin 2,3-dioxygenase, which contains copper Cu having 3 His and 1 Glu, both the Glu-bound and unbound forms are concomitantly observed in the Cu 2þ state [58,59].…”

The Crucial Importance of Chemistry in the Structure−Function Link: Manipulating Hydrogen Bonding in Iron-Containing Superoxide Dismutase,

“…These and other mutations of the active site Gln also significantly alter the E m (10,22,25,26), consistent with our proposal that the H-bond between Gln69 and coordinated solvent exerts an important influence on the relative stabilities of coordinated H 2 O vs OH -and, thereby, the E m (1,10,22). Since proton transfer coupled to electron transfer is the norm in biological chemistry, we proposed that proteins' exquisite and strong control over the pKs and degrees of protonation of functionalities coupled to the redox sites, can provide a general and very important mechanism of redox tuning in enzymes (27,57).…”

A Single Outer-Sphere Mutation Stabilizes apo-Mn Superoxide Dismutase by 35 °C and Disfavors Mn Binding

“…23–25 The coordinated solvent molecule is central to an active site H-bond network that connects it to bulk solvent via a second-sphere glutamine (Gln146 in E. coli MnSOD or Gln69 in E. coli FeSOD) which H-bonds with the hydroxyl of conserved Tyr34 which in turn H-bonds with a solvent molecule in the channel connecting the active site to bulk solvent (Figure 1). 15, 26–30 The most highly-conserved difference between FeSODs and MnSODs is the origin of the Gln residue (or in some cases His) 1, 3 that H-bonds to coordinated solvent. 5, 31–33 MnSODs contribute the conserved Gln146 from a position between a beta strands in the C-terminal domain (Figure 1) whereas FeSODs contribute Gln69 from an alpha helix in the N-terminal domain (Supplemental Figure S1).…”