Current Pharmaceutical Design - Volume 15, Issue 20, 2009

From cancer to obesity to bacterial infections, dysregulation of metalloproteinases, can be a causative factor in disease states. A subclass of metalloproteinases, the metzincins, defines a super family that is involved in a number of pathophysiological conditions. Each member contains a HEXGHXXGXXHD region that coordinates the active site zinc atom and is critical for catalysis. In addition, they also have a structural mo Read More

While it is highly accepted that ADAM family members with ubiquitous expression patterns, such as ADAM10 and ADAM17 have major roles in homoeostasis and pathology, ADAM8 was initially considered as an immune-specific ADAM with a cell-specific expression pattern. Therefore, ADAM8 had a “sleeping beauty” existence for many years, and has recently come back into focus as it was detected under several path Read More

ADAM (a disintegrin and metalloproteinase) proteins have a predominant role in the protein ectodomain shedding of membrane-bound molecules. ADAMs have emerged as critical regulators of cell-cell signaling during development and homeostasis, and are believed to contribute to pathologies, such as cancer, where their regulation is altered. ADAM9 is consistently overexpressed in various human cancers, and plays Read More

Both cancer and chronic inflammatory diseases are often marked by homeostatic signal transduction pathways run amok. Cleavage of membrane-bound substrates by extracellular metalloproteinases is frequently the rate limiting step in activating many of these pathways, resulting either in liberation of active ligands (shedding) or initiating further processing into bioactive cytoplasmic domains (regulated intramembrane prot Read More

ADAM12/meltrin α is a type I transmembrane multidomain protein involved in tumor progression and other severe diseases, including osteoarthritis, and as such could be considered as a potential drug target. In addition to protease activity, ADAM12 possesses cell binding and cell signaling properties. This functional trinity is reflected in the structure of ADAM12, which can be divided into head, body, and tail. The he Read More

ADAM15 is a widely expressed multi-domain protease that has been implicated in the pathogenesis of many human diseases. Given the diversity of the ADAM15 functional domains, this protease is thought to affect several important cellular processes, including cell adhesion, degradation of extracellular matrix components, and ectodomain shedding of membrane-bound growth factors that are intrinsic to cancer and various Read More

As a metalloproteinase specialized in releasing membrane-tethered proteins, A Disintegrin and A Metalloproteinase 17 (ADAM17), also known as Tumor necrosis factor-α Converting Enzyme (TACE) or less commonly CD156q, has received more than its share of attention. This is mainly because major contemporary pathologies like cancer, inflammatory and vascular diseases seem to be connected to its cleavage abilities. The inv Read More

A disintegrin and metalloproteinase 19 (ADAM19, or adamalysin 19) is a cell surface glycoprotein with a signal sequence, a prodomain, a metalloproteinase domain, a disintegrin domain, a cysteine-rich domain, a epidermal growth factor-like domain, a transmembrane domain, and a cytoplasmic domain. It is an endopeptidase that cleaves extracellular matrix proteins and sheds growth factors and cytokines such as ne Read More

ADAM28 is a member of the ADAM (a disintegrin and metalloproteinase) gene family and consists of two isoforms, prototype membrane-type form and short secreted form. The metalloproteinase domain of ADAM28 has the zincbinding consensus sequence, andADAM28 exhibits catalytic activity to a few substrates such as insulin-like growth factor binding protein-3. The disintegrin domain interacts with integrins α4β1, α4β7 and α Read More

The a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family of metalloproteases consists of 19 members. These enzymes play an important role in the turnover of extracellular matrix proteins in various tissues and their altered regulation has been implicated in diseases such as cancer, arthritis and atherosclerosis. Unlike other metalloproteinases, ADAMTS members demonstrate a narrow substrate speci Read More