IMR Press / FBL / Volume 9 / Issue 5 / DOI: 10.2741/1436

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Structure-based development of a novel collagen inhibitor for MMP-1: re-designing the functions of a matrix protein
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1 Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404
2 Harvard Center for Neurodegeneration and Repair, 65 Landsdowne Street, Cambridge, MA 02139
Academic Editor:Mathew Pincus
Front. Biosci. (Landmark Ed) 2004, 9(5), 2788–2795;
Published: 1 September 2004

Collagenases are a highly specific class of enzymes (1). In their native states, collagenases cleave only native triple helical collagen molecules at a single peptide bond between Gly775-Leu776 for Type I collagen and Gly775-Ile776 for Type II collagen (1, 2, 3). The linear sequence of collagen is about 1050 amino acids in length, where three linear peptide sequences are required to form a triple helical collagen molecule. At present, there exist no crystallographic structures of collagenase bound to native triple helical collagen; nor has it been shown that collagenase recognizes the triple helical conformation of collagen. In our study, we have used an inhibitor design structure-activity based approach to show that collagenase recognizes and cleaves triple helical collagen conformations in preference to non-triple helical collagen conformations (4).

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