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PDBsum entry 2mop
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References listed in PDB file
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Key reference
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Title
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Nmr structure of bitistatin – a missing piece in the evolutionary pathway of snake venom disintegrins.
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Authors
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R.J.Carbajo,
L.Sanz,
A.Perez,
J.J.Calvete.
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Ref.
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Febs J, 2015,
282,
341-360.
[DOI no: ]
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PubMed id
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Abstract
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Extant disintegrins, as found in the venoms of Viperidae and Crotalidae snakes
(vipers and rattlesnakes, represent a family of polypeptides that block the
function of β1 and β3 integrin receptors, both potently and with a high degree
of selectivity. This toxin family owes its origin to the neofunctionalization of
the extracellular region of an ADAM (a disintegrin and metalloprotease) molecule
recruited into the snake venom gland proteome in the Jurassic. The evolutionary
structural diversification of the disintegrin scaffold, from the ancestral long
disintegrins to the more recently evolved medium-sized, dimeric and short
disintegrins, involved the stepwise loss of pairs of class-specific disulfide
linkages and the processing of the N-terminal region. NMR and crystal structures
of medium-sized, dimeric and short disintegrins have been solved. However, the
structure of a long disintegrin remained unknown. The present study reports the
NMR solution structures of two disulfide bond conformers of the long disintegrin
bitistatin from the African puff adder Bitis arietans. The findings provide
insight into how a structural domain of the extracellular region of an ADAM
molecule, recruited into and selectively expressed in the snake venom gland
proteome as a PIII metalloprotease in the Jurassic, has subsequently been
tranformed into a family of integrin receptor antagonists.
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