Title:Crystal Structure of a Cu,Zn Superoxide Dismutase From the Thermophilic Fungus Chaetomium thermophilum
Volume: 28
Issue: 9
Author(s): Imran Mohsin, Li-Qing Zhang, Duo-Chuan Li*Anastassios C. Papageorgiou*
Affiliation:
- Department of Mycology, Shandong Agricultural University, Taian, Shandong 271018,China
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku 20521,Finland
Keywords:
Enzyme stability, Chaetomium thermophilum, metal binding, superoxide, thermophilic fungus, crystal structure.
Abstract:
Background: Thermophilic fungi have recently emerged as a promising source of thermostable
enzymes. Superoxide dismutases are key antioxidant metalloenzymes with promising
therapeutic effects in various diseases, both acute and chronic. However, structural heterogeneity
and low thermostability limit their therapeutic efficacy.
Objective: Although several studies from hypethermophilic superoxide dismutases (SODs) have
been reported, information about Cu,Zn-SODs from thermophilic fungi is scarce. Chaetomium thermophilum
is a thermophilic fungus that could provide proteins with thermophilic properties.
Methods: The enzyme was expressed in Pichia pastoris cells and crystallized using the vapor-diffusion
method. X-ray data were collected, and the structure was determined and refined to 1.56 Å resolution.
Structural analysis and comparisons were carried out.
Results: The presence of 8 molecules (A through H) in the asymmetric unit resulted in four different
interfaces. Molecules A and F form the typical homodimer which is also found in other Cu,Zn-
SODs. Zinc was present in all subunits of the structure while copper was found in only four subunits
with reduced occupancy (C, D, E and F).
Conclusion: The ability of the enzyme to form oligomers and the elevated Thr:Ser ratio may be
contributing factors to its thermal stability. Two hydrophobic residues that participate in interface
formation and are not present in other CuZn-SODs may play a role in the formation of new interfaces
and the oligomerization process. The CtSOD crystal structure reported here is the first
Cu,Zn-SOD structure from a thermophilic fungus.