http://www.mdpi.com/journal/toxins/special_issues/disintegrins/ Dear Colleagues, Disintegrins are interesting molecules isolated as soluble proteins from snake venom. They are isolated from venom of different species in a variety of forms varying from short to medium to long polypeptide chains of approximately 49, 67 and 84 amino acids, respectively. Additionally, they are also found as homodimers or heterodimers with two identical or dissimilar chains, respectively, held together by two disulfide bonds. The structure of several disintegrins has been determined by solution NMR or X-ray crystallography. Interestingly, structural determination of one homodimeric disintegrin revealed that the two Arg-Gly-Asp (RGD) motifs on the individual chains are separated by 69Ǻ. In the monomeric and dimeric disintegrins the RGD motif is exposed in a 13 amino acid flexible loop that enables the disintegrins to bind with high affinity to integrins. Disintegrins have interesting antagonist/agonist activity towards integrins and this has been taken advantage of in developing anti-tumor and anti-angiogenic strategies for the use of disintegrins. In animal models of breast, ovarian and prostate cancer and glioma, disintegrins have shown portent anti-tumor activity and studies are also underway to use disintegrins as imaging agents for cancer diagnostic purposes as well. Another class of disintegrin-containing proteins is the ADAM (A Disintegrin And Metalloproteinase) family. These proteins, which represent the only mammalian proteins known to contain a disintegrin domain, are transmembrane proteins. The extracellular disintegrin domain may bind to integrins to facilitate metalloproteinase catalyzed events. Dr. Frank S. MarklandDr. Radu Minea Dr. Steve Swenson Guest Editors {snippet name="submission_info"} http://www.mdpi.com/2072-6651/2/11/2606/ Cell migration is a key process for the defense of pluricellular organisms against pathogens, and it involves a set of surface receptors acting in an ordered fashion to contribute directionality to the movement. Among these receptors are the integrins, which connect the cell cytoskeleton to the extracellular matrix components, thus playing a central role in cell migration. Integrin clustering at focal adhesions drives actin polymerization along the cell leading edge, resulting in polarity of cell movement. Therefore, small integrin-binding proteins such as the snake venom disintegrins that inhibit integrin-mediated cell adhesion are expected to inhibit cell migration. Here we review the current knowledge on disintegrin and disintegrin-like protein effects on cell migration and their potential use as pharmacological tools in anti-inflammatory therapy as well as in inhibition of metastatic invasion. http://www.mdpi.com/2072-6651/2/11/2606/ Fri, 29 Oct 2010 00:00:00 CEST Toxins 2010-10-29 2 11 Review 2606 2621 2072-6651 Snake Venom Disintegrins and Cell Migration 2010-10-29 doi: 10.3390/toxins2112606 Heloisa S. Selistre-de-Araujo Carmen L. S. Pontes Cyntia F. Montenegro Ana Carolina B. M. Martin http://www.mdpi.com/2072-6651/2/10/2411/ The ADAM (a disintegrin-like and metalloproteinase) proteins are a family of transmembrane cell-surface proteins with important functions in adhesion and proteolytic processing in all animals. Human ADAM-15 is the only member of the ADAM family with the integrin binding motif Arg-Gly-Asp (RGD) in its disintegrin-like domain. This motif is also found in most snake venom disintegrins and other disintegrin-like proteins. This unique RGD motif within ADAM-15 serves as an integrin ligand binding site, through which it plays a pivotal role in interacting with integrin receptors, a large family of heterodimeric transmembrane glycoproteins. This manuscript will present a review of the RGD-containing disintegrin-like domain structures and the structural features responsible for their activity as antagonists of integrin function in relation to the canonical RGD template. http://www.mdpi.com/2072-6651/2/10/2411/ Tue, 19 Oct 2010 00:00:00 CEST Toxins 2010-10-19 2 10 Review 2411 2427 2072-6651 ADAM-15 Disintegrin-Like Domain Structure and Function 2010-10-19 doi: 10.3390/toxins2102411 Dong Lu Mike Scully Vijay Kakkar Xinjie Lu