Probing the role of proline -135 on the structure, stability, and cell proliferation activity of human acidic fibroblast growth factor

Archives of Biochemistry and Biophysics
Julie Eberle DavisThallapuranam Krishnaswamy Suresh Kumar

Abstract

Human acidic fibroblast growth factor 1 (hFGF1) is a protein intricately involved in cell growth and tissue repair. In this study, we investigate the effect(s) of understanding the role of a conserved proline (P135), located in the heparin binding pocket, on the structure, stability, heparin binding affinity, and cell proliferation activity of hFGF1. Substitution of proline-135 with a positively charged lysine (P135K) resulted in partial destabilization of the protein; however, the overall structural integrity of the protein was maintained upon substitution of proline-135 with either a negative charge (P135E) or a polar amino acid (P135Q). Interestingly, upon heparin binding, an increase in thermal stability equivalent to that of wt-hFGF1 was observed when P135 was replaced with a positive (P135K) or a negative charge (P135E), or with a polar amino acid (P135Q). Surprisingly, introduction of negative charge in the heparin-binding pocket at position 135 (P135E) increased hFGF1's affinity for heparin by 3-fold, while the P135K mutation, did not alter the heparin-binding affinity. However, the enhanced heparin-binding affinity of mutant P135E did not translate to an increase in cell proliferation activity. Interestingly, the P135K...Continue Reading

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Mar 21, 2018·Biochemistry and Biophysics Reports·Julie Eberle DavisThallapuranam Krishnaswamy Suresh Kumar

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Citations

Aug 20, 2019·Biochemical and Biophysical Research Communications·Rebecca KerrThallapuranam Krishnaswamy Suresh Kumar
Oct 14, 2020·Current Drug Targets·Shilpi AgrawalThallapuranam Krishnaswamy Suresh Kumar

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