Insight into the Stability of LOXL2: a Computational Study.

Lysyl oxidase-like 2 (LOXL2) is a Cu2+-dependent amine oxidase, and it catalyzes the oxidative deamination of the ε-amino group of Lys residues on elastin and collagen, which is critical for extracellular matrix modeling. Stability is an important property for protein and it directly affects the dynamics and function of protein, which strongly relates to the human health and disease. However, the stability of LOXL2 is not well defined, i.e., which residues are important for its stability is unclear. In this paper, protein stability of LOXL2 was calculated by four methods, viz. mCSM, PremPS, DeepDDG and FoldX. Our results indicate that 95 residues (key residues) are important for the stability of LOXL2, with the amount of 14, 13, 8, 11, 26 in domain 1, 2, 3, 4, 5, respectively, while 23 in the linker between domains. Among these key residues, the types (numbers) are Leu (24), Val (20), Ile (12), Trp (11), Phe (11), Tyr (6), Cys (6), Met (4) and Arg (1). Most of the key residues are hydrophobic (88 in 95), which is consistent with the fact that hydrophobic interaction is the main force in protein folding. Cys residues are paired to constitute disulfide bonds, which play an important role in the structure and function of LOXL2. In the discussion, we compare the results with experimental data, and use the free energy perturbation for verification, which prove the reliability of this work. Thus, this study provides important insight for the research of disease treatment targeting LOXL2. [ABSTRACT FROM AUTHOR]