Solution Structure of a Novel Disintegrin, Salmosin, from Agkistrondon halys Venom

Joon Shin, Sung Yu Hong, Kwanghoe Chung, Incheol Kang, Yangsoo Jang, Doo Sik Kim, Weontae Lee

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Disintegrins are potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion. A new disintegrin, salmosin, isolated from the venom of the Korean snake Agkistrodon halys brevicaudus, has been characterized by mass spectrometry and NMR spectroscopy, and its in vitro biological activity has been assessed. The IC50 value of the purified salmosin was determined to be 2.2 nM in an assay for the inhibition of glycoprotein IIb-IIIa/fibrinogen interaction. Salmosin also inhibited the bovine capillary endothelial cell proliferation induced by bFGF in a dose-dependent manner. The NMR solution structures were well converged with a root-mean-square deviation of 0.76 Å for backbone atoms among the 20 lowest energy structures, except for the arginylglycylaspartic acid (RGD) loop. The structure revealed that the conserved RGD motif with an unusual finger shape is distal from the rigid core of the C-terminal domain. Furthermore, even though the RGD motif did not interact with the hydrophobic core of the protein, it was stabilized by a network of molecular contacts through a small antiparallel β-sheet comprising residues of Ile46-Ala50 and Asp54-Tyr58. Last, the electrostatic charge distribution on the surface of salmosin differs dramatically from that of other disintegrin proteins in that there is a cluster of negatively charged residues in close proximity to the RGD loop.

Original languageEnglish
Pages (from-to)14408-14415
Number of pages8
JournalBiochemistry
Volume42
Issue number49
DOIs
Publication statusPublished - 2003 Dec 16

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Disintegrins
Venoms
Mass Spectrometry
Agkistrodon
Platelet Glycoprotein GPIIb-IIIa Complex
Snake Venoms
Platelet Aggregation Inhibitors
Charge distribution
Cell adhesion
Endothelial cells
Cell proliferation
Bioactivity
Static Electricity
Cell Adhesion
Integrins
Fibrinogen
Nuclear magnetic resonance spectroscopy
Inhibitory Concentration 50
Fingers
Mass spectrometry

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Shin, Joon ; Hong, Sung Yu ; Chung, Kwanghoe ; Kang, Incheol ; Jang, Yangsoo ; Kim, Doo Sik ; Lee, Weontae. / Solution Structure of a Novel Disintegrin, Salmosin, from Agkistrondon halys Venom. In: Biochemistry. 2003 ; Vol. 42, No. 49. pp. 14408-14415.
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Solution Structure of a Novel Disintegrin, Salmosin, from Agkistrondon halys Venom. / Shin, Joon; Hong, Sung Yu; Chung, Kwanghoe; Kang, Incheol; Jang, Yangsoo; Kim, Doo Sik; Lee, Weontae.

In: Biochemistry, Vol. 42, No. 49, 16.12.2003, p. 14408-14415.

Research output: Contribution to journalArticle

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AU - Hong, Sung Yu

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