Special Issue "Disintegrins: Structure-Function and Translational Potential"
A special issue of Toxins (ISSN 2072-6651).
Deadline for manuscript submissions: closed (31 August 2011)
Prof. Dr. Frank S. Markland
Department of Biochemistry and Molecular Medicine and Comprehensive Cancer, Center, University of Southern California, Keck School of Medicine, Hoffman Medical Research Building #813, 2011 Zonal Ave., Los Angeles, CA 90089, USA
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Phone: +(323) 442-2747
Interests: protein chemistry and structure/ function interrelationships; snake venom components with procoagulant and anticoagulant activities; snake venom platelet aggregation inhibitors (disintegrins); disintegrins as anti-angiogenic agents; disintegrins and wound healing; disintegrins as bioadhesive agents
Dr. Radu Minea
Department of Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine, USA
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. Markland
Dr. Radu Minea
Dr. Steve Swenson
- snake venom
- signal transduction pathways
- clinical translation