ABSTRACT
The matrix metalloproteinases (MMPs) are a family of ubiquitous enzymes that are involved in extracellular matrix degradation and remodeling. The MMP enzyme family is part of the superfamily of metzincins. The MMPs are secreted as inactive proenzymes, which are activated by proteolytic cleavage. The MMPs consist of one or more structural domains. The first domain, the propeptide domain, confers a self-inhibitory action on the full-length MMP. The second domain contains the active site residues and is referred to as the catalytic domain. The remainder of the MMPs also contain a hemopexin-like domain connected to the catalytic domain by a proline-rich linker. As a model case of structure-based drug design for MMPs the authors look at the design of a right-handed inhibitor based on the x-ray structures of fibroblast collagenase and neutrophil collagenase. The design of active-site inhibitors based on the natural substrate of the collagenases has produced a variety of zinc-binding groups to anchor the inhibitor to the catalytic zinc.
