Binding as a Rate-Limiting Step for Substrate Recognition of ADAM17

Abstract:

ADAM17 is an important membrane-bound proteinase, and it can release a lot of proteins from their membrane-bound forms, such as cytokines, cytokine receptors and adhesion proteins. ADAM17 has long been an interesting therapeutic target in a lot of diseases; however, the development of its inhibitors has been hurdled by our very limited knowledge on its substrate specificity and selectivity. To understand the substrate specificity of ADAM17, here in this paper, a rational complex model is computationally built for the catalytic domain of ADAM17 and its recognizing sequence from the TNF-alpha precursor (proTNF-alpha). With protein-peptide docking analysis, we found that the substrate binding step is indeed important for ADAM17 recognition and processing. The result in this paper could be useful for the understanding of the substrate specificity and selectivity, and the design of novel ADAM17 inhibitors in the future.

• Periodical: Advanced Materials Research (Volume 717)
• Pages: 244-248
• DOI: https://doi.org/10.4028/www.scientific.net/AMR.717.244
• Online since: July 2013
• Authors: Liu Sen, Xiao Hong Ma
• Keywords: ADAM17, Metalloproteinase, Protein-Peptide Docking, Substrate Recognition, TACE

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