Computational design of Matrix Metalloprotenaise-9 (MMP-9) resistant to auto-cleavage.

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-9 _Cat ) 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-9 _Cat variant that is active but stable to autocleavage. For this purpose, we first identified potential autocleavage sites on MMP-9 _Cat using mass spectroscopy and then eliminated the autocleavage site by predicting mutatio

SUBMITTER: Bonadio A 

PROVIDER: S-EPMC10120622 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature