Based on structural information of iron superoxide dismutase (Fe-SOD), we constructed
various types of Fe-SOD amino acid networks (Fe-SOD AANs). Analyses of the degree of distribution
and "rich clubs" of these Fe-SOD AANs indicated that Fe-SOD AANs have highly interacting nodes,
namely, the hubs. Interestingly, most hubs are hydrophobic amino acids including Ile, Leu, Phe, Ala
and Val. These residues form a strong hydrophobic core that improves Fe-SOD structural stability.
Most hubs are uniformly distributed in evolutionally conserved regular secondary structures to maintain Fe-SOD
biological functionality. Moreover, a comparison of hubs in several Fe-SOD ANNs with different thermostability revealed
that hydrophobic amino acids, such as Gly, Leu, and Phe, but not Gln and Thr, have more interactions and form hubs and
is therefore conducive to a more highly hydrophobic core and denser packing of thermostable Fe-SOD. Total numbers of
hubs, numbers of hubs in 3/10 helices, turn structures and especially in alpha helices, and the ratio of inner hubs in
secondary structure are all important factors for Fe-SOD thermostability. Mutating hub residues on the Fe-SOD surface
can improve Fe-SOD thermostability because of increasing hydrogen bond interactions. The results also show hubs in
AAN can be used to study the relationship between protein structural characteristic and stability.