Design of variants of human fibroblast growth factor 1 with enhanced stability and cell proliferation activity

Abstract

Human Fibroblast growth factor 1 (hFGF1) is a member of FGF1 subfamily which play significant biological roles, including cell proliferation, cell differentiation, and wound healing. Under physiological temperatures, hFGF1 has low thermodynamic stability and susceptible to the action of proteases. Circular dichroism, fluorescence spectroscopy, and other related studies reveal that reversal of charge on R136 by acidic amino acids (Glu) drastically increases the enzymatic resistance to thrombin, thermal stability, and cell proliferation activity of the growth factor. Interestingly, introduction of R136D mutation shows that the protein stability and cell proliferation activity is similar to the wild‐type protein. Microsecond molecular dynamics studies suggest that length of the side chain of acidic amino acid at position 136 is critical to confer stability to the protein. Detailed analysis of the results will be presented.