1ZA5

Q69H-FeSOD

Summary for 1ZA5

• Entry DOI: 10.2210/pdb1za5/pdb
• Related: 1ISB 1IsA
• Descriptor: Superoxide dismutase [Fe], FE (III) ION, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total)
• Functional Keywords: h-bonding redox tuning superoxide dismutase proton-coupled electron transfer, oxidoreductase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 42929.27

Authors

Yikilmaz, E.,Rodgers, D.W.,Miller, A.F. (deposition date: 2005-04-05, release date: 2006-03-14, Last modification date: 2024-02-14)

Primary citation

Yikilmaz, E.,Rodgers, D.W.,Miller, A.F.
The Crucial Importance of Chemistry in the Structure-Function Link: Manipulating Hydrogen Bonding in Iron-Containing Superoxide Dismutase.
Biochemistry, 45:1151-1161, 2006

PubMed Abstract: Fe-containing superoxide dismutase's active site Fe is coordinated by a solvent molecule, whose protonation state is coupled to the Fe oxidation state. Thus, we have proposed that H-bonding between glutamine 69 and this solvent molecule can strongly influence the redox activity of the Fe in superoxide dismutase (SOD). We show here that mutation of this Gln to His subtly alters the active site structure but preserves 30% activity. In contrast, mutation to Glu otherwise preserves the active site structure but inactivates the enzyme. Thus, enzyme function correlates not with atom positions but with residue identity (chemistry), in this case. We observe strong destabilization of the Q69E-FeSOD oxidized state relative to the reduced state and intermediate destabilization of oxidized Q69H-FeSOD. Indeed, redox titrations indicate that mutation of Gln69 to His increases the reduction potential by 240 mV, whereas mutation to Glu appears to increase it by more than 660 mV. We find that this suffices to explain the mutants' loss of activity, although additional factors may also contribute. The strongly elevated reduction potential of Q69E-FeSOD may reflect reorganization of the active site H-bonding network, including possible reversal of the polarity of the key H-bond between residue 69 and coordinated solvent.

PubMed: 16430211
DOI: 10.1021/bi051495d

Experimental method

X-RAY DIFFRACTION (1.8 Å)