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Snake venom disintegrins: evolution of structure and function
Authors:Juan J. Calvete, Cezary Marcinkiewicz, Daniel Monle  n, Vicent Esteve, Bernardo Celda, Paula Ju  rez,Libia Sanz
Affiliation:

aInstituto de Biomedicina de Valencia, C.S.I.C., Jaume Roig 11, 46010 Valencia, Spain

bDepartment of Biology, Center for Neurovirology and Cancer Biology, Temple University, N. 12th Street, Philadelphia, PA 19122, USA

cDepartamento de Química Física, Universitat de València, Dr Moliner 50, 46100 Burjassot (Valencia), Spain

dServicio Central de Soporte a la Investigación Experimental, Universitat de València, Dr Moliner 50, 46100 Burjassot (Valencia), Spain

Abstract:
Disintegrins represent a family of polypeptides present in the venoms of various vipers that selectively block the function of integrin receptors. Here, we review our current view and hypothesis on the emergence and the structural and functional diversification of disintegrins by accelerated evolution and the selective loss of disulfide bonds of duplicated genes. Research on disintegrins is relevant for understanding the biology of viper venom toxins, but also provides information on new structural determinants involved in integrin recognition that may be useful in basic and clinical research. The role of the composition, conformation, and dynamics of the integrin inhibitory loop acting in concert with the C-terminal tail in determining the selective inhibition of integrin receptors is discussed.
Keywords:Snake venom proteins   Disintegrins   Integrin antagonists   Structure-function correlations   Evolution of protein structure   Disulfide bond engineering
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