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Title: | Computational design of Matrix Metalloprotenaise-9 (MMP-9) resistant to auto-cleavage |
Authors: | Bonadio, Alessandro |
Keywords: | protein; phân hủy; phân cắt; metallicoproteinase |
Issue Date: | 2023 |
Publisher: | bioRxiv |
Abstract: | Matrix metalloproteinase-9 (MMP-9) is an endopeptidase that remodels the extracellular matrix and has been implicated as a major driver in cancer metastasis. Hence, there is a high demand for MMP-9 inhibitors for therapeutic purposes. For such drug design efforts, large amounts of MMP-9 are required. Yet, the catalytic domain of MMP-9 (MMP-9Cat) is an intrinsically unstable enzyme that tends to auto-cleave within minutes, making it difficult to use in drug design experiments and other biophysical studies. We set our goal to design MMP-9Cat variant that is active but stable to autocleavage. For this purpose, we first identified potential autocleavage sites on MMP-9Cat using mass spectroscopy and then eliminated the autocleavage site by predicting mutations that minimize autocleavage potential without reducing enzyme stability. |
URI: | http://dlib.hust.edu.vn/handle/HUST/23388 |
Link item primary: | https://www.biorxiv.org/content/10.1101/2023.04.11.536383v1.full.pdf+html |
Appears in Collections: | OER - Kỹ thuật hóa học; Công nghệ sinh học - Thực phẩm; Công nghệ môi trường |
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