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

Calvete, Juan J., Moreno-Murciano, M. Paz, Theakston, R.David G., Kisiel, Dariusz G. and Marcinkiewicz, Cezary (2003) 'Snake venom disintegrins: novel dimeric disintegrins and structural diversification by disulphide bond engineering'. Biochemical Journal, Vol 372, pp. 725-734.

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Abstract

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 a5b1 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 a4b1 integrin to vascular cell adhesion molecule 1 with high selectivity. On the other hand, disintegrin EMS11 inhibited both a5b1 and a4b1 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.

Item Type:	Article
Additional Information:	The final version of record is available at www.biochemj.org
Subjects:	QU Biochemistry > Cells and Genetics > QU 350 Cellular structures QU Biochemistry > Proteins. Amino Acids. Peptides > QU 58.5 DNA. WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles
Digital Object Identifer (DOI):	https://doi.org/10.1042/bj20021739
Depositing User:	Users 476 not found.
Date Deposited:	31 Jan 2013 16:41
Last Modified:	22 Nov 2024 14:35
URI:	https://archive.lstmed.ac.uk/id/eprint/2510

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