Superoxide Dismutases from hyperThermophiles

 

Geoffrey B. Jameson,a Julian J. Adams,a Paul D. Hempstead,a Irene Morgenstern-Badarau,b James W. Whittaker,c Edward N. Bakerd and Bryan F. Andersona

 

aCentre for Structural Biology, Institutes of Fundamental Sciences and Molecular BioSciences, Massey University, Palmerston North, New Zealand; bInstitut de Chimie Moleculaire dOrsay, Bat. 420 Universit Paris-Sud XI, 91405 Orsay, France; cDepartment of Biochemistry and Molecular Biology, Oregon Graduate Institute School of Science and Engineering, Beaverton, Oregon 97006, USA; dSchool of Biological Sciences, University of Auckland, Auckland, New Zealand (G.B.Jameson@massey.ac.nz)

 

 

The structures of the apo, Fe and Mn forms of the manganese-preferring superoxide dismutase from the hyperthermophilic microaerobic archaeon Pyrobaculum aerophilum (Pa-SOD) have been determined at 2.0, 2.2 and 1.9 , respectively, and the structure of the Fe-specific superoxide dismutase from the thermophilic methanogenic anerobic archaeon Methanobacterium thermoautotrophicum (Mt-FeSOD) has been determined at 2.6 . Corresponding values for R (Rfree) are, presently, 0.16 (0.20), 0.19 (0.24), 0.17 (0.20), and 0.22 (0.24); the asymmetric unit is a dimer for Pa-SODs and a tetramer and half-tetramer for Mt-FeSOD. 

The extreme thermal stability of Pa-SOD, which survives the autoclaving necessary to insert metal ions into the E. coli-expressed apo-protein, appears to arise from a combination of previously identified structural determinants for thermal stability. In particular, both the Pa-SODs and the Mt-FeSOD form extremely compact tetramers.

In common with all other structurally characterised Mn- and FeSODs, the central metal ions of Pa-FeSOD, Pa-MnSOD and Mt-FeSOD have an identical primary coordination sphere. Three histidines, a monodentate aspartate and a solvent-derived ligand (OH- in oxidised MIII forms) coordinate in a trigonal bipyramidal manner, in which the solvent-derived ligand and a histidine ligand are trans to each other. No differences exist in the second coordination sphere for both species a histidine C-H moiety hydrogen bonds to the solvent-derived ligand, although in many other SODs this aprotic C-H moiety is substituted by a glutamine NH2 moiety. It is only in the third coordination sphere, involving the hydrogen-bonding network to the amine moiety of the coordinated axial histidine that significant differences can be found not only for these SODs but also for other SODs that have been well-characterised both structurally and functionally. A methionine thioether moiety appears to direct a different hydrogen-bonding network to the axial histidine for Mn-specific SODs, in contrast to Fe-specific SODs where an aliphatic residue is found at this location, position n on the helix supporting the axial histidine at position n+3.