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Snake venom disintegrins: novel dimeric disintegrins and structural diversification by disulphide bond engineering

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dc.creator Calvete, Juan J.
dc.creator Moreno-Murciano, Paz
dc.creator Theakston, R David G
dc.creator Kisiel, Dariusz G
dc.creator Marcinkiewicz, Cezary
dc.date 2008-04-16T16:03:41Z
dc.date 2008-04-16T16:03:41Z
dc.date 2003-06-15
dc.date.accessioned 2017-01-31T01:02:28Z
dc.date.available 2017-01-31T01:02:28Z
dc.identifier Biochem J. 2003 June 15; 372(Pt 3): 725–734
dc.identifier http://dx.doi.org/10.1042/BJ20021739
dc.identifier 0264-6021
dc.identifier http://hdl.handle.net/10261/3631
dc.identifier 10.1042/BJ20021739.
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3631
dc.description The final version of record is available at: http://www.biochemj.org/bj/default.htm
dc.description We report the isolation and amino acid sequences of six novel dimeric disintegrins from the venoms of Vipera lebetina obtusa (VLO), V. berus (VB), V. ammodytes (VA), Echis ocellatus (EO) and Echis multisquamatus (EMS). Disintegrins VLO4, VB7, VA6 and EO4 displayed the RGD motif and inhibited the adhesion of K562 cells, expressing the integrin alpha5beta1 to immobilized fibronectin. A second group of dimeric disintegrins (VLO5 and EO5) had MLD and VGD motifs in their subunits and blocked the adhesion of the alpha4beta1 integrin to vascular cell adhesion molecule 1 with high selectivity. On the other hand, disintegrin EMS11 inhibited both alpha5beta1 and alpha4beta1 integrins with almost the same degree of specificity. Comparison of the amino acid sequences of the dimeric disintegrins with those of other disintegrins by multiple-sequence alignment and phylogenetic analysis, in conjunction with current biochemical and genetic data, supports the view that the different disintegrin subfamilies evolved from a common ADAM (a disintegrin and metalloproteinase-like) scaffold and that structural diversification occurred through disulphide bond engineering.
dc.description This work was financed by the Dirección General de Enseñanza Superior e Investigación Científica (Madrid, Spain) (grant no. BMC2001-3337; to J. J. C.) and the American Heart Association (Dallas, TX, U.S.A.; to C. M.).
dc.description Peer reviewed
dc.format 510722 bytes
dc.format application/pdf
dc.language eng
dc.publisher Biochemical Society
dc.rights openAccess
dc.subject Disintegrin
dc.subject Disulphide bond
dc.subject Evolution
dc.subject Protein sequence
dc.subject Snake venom protein
dc.title Snake venom disintegrins: novel dimeric disintegrins and structural diversification by disulphide bond engineering
dc.type Artículo


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