3.1 Structure analysis of surface cysteine of IL-18
Although the analysis of cysteine residues on the surface area of IL-18
was described in the previous work (Yamamoto et al., 2004, p. 18), the
source of PDB structure was from NMR analysis (PDB no. 1J0S) (Kato et
al., 2003, p. 18). Currently, IL-18 structure was crystalized together
with its receptors (Tsutsumi et al., 2014, p. 18) allowing the
researchers to study the role of each amino acid residue of human IL-18
on its interaction to the receptor. We decided to re-analyze the role of
surface cysteine on its interaction to receptor by using crystalized
structure (PDB no. 3WO3). As showed in Fig. 1A and 1B, the surface
cysteine including C38, C68, C76 and C127 can be found independently and
are not interacted to each other. The direction of thiol side chain of
most cysteine showed toward the surface of IL-18 molecule. No
intramolecular interaction was found suggesting the role of these
surface cysteine for intermolecular interaction. Additionally, when the
analysis of these amino acids was considered in binding mode with its
receptor, IL-18 receptor α, all of these cysteines were not found to be
important for the receptor binding (Fig. 1B). This is in accordance with
the analysis from the NMR structure that showed the possibility of amino
acid replacement did not disrupt the interaction between IL-18 and IL-18
receptors (Yamamoto et al., 2004). Therefore, we applied the mutation
from this work to improve our engineered human IL-18.