Chloramine T‐induced structural and biochemical changes in echistatin

FEBS Letters

Chandra Kumar, C.¹  Nie, Huiming¹  Vijay-Kumar, Senadhi²  Tsarbopoulos, Anthony¹  Armstrong, Lydia¹  Zhang, Rumin¹ 

[1] Departments of Tumor Biology, Structural chemistry, Schering-Plough Research Institute, 2015, Galloping Hill Road, Kenilworth, NJ 07033, USA;FELS Institute for Cancer Research and Molecular Biology, Temple University School Of Medicine, Philadelphia, PA 19140, USA

关键词: Echistatin;    Integrin receptor;    Chloramine T;    Oxidation;    RGD motif;   

DOI  :  10.1016/S0014-5793(98)00587-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Echistatin is a member of the disintegrin family of peptides and a potent inhibitor of platelet aggregation and cell adhesion. Echistatin binds to integrin α_vβ₃ and α_IIbβ₃ receptors with high affinity. Binding is mediated by an RGD-containing loop maintained in an appropriate conformation by disulfide bridges. In this study, we have compared the binding characteristics of echistatin iodinated by either lactoperoxidase or chloramine T method. We show that echistatin labeled by lactoperoxidase method binds to integrin α_vβ₃ receptor with high affinity and in a non-dissociable manner very similar to native echistatin. In contrast, chloramine T-labeled echistatin can rapidly dissociate from the receptor. We demonstrate that chloramine T reaction results in the addition of an extra oxygen to the methionine residue adjacent to the RGD motif in echistatin. Modeling studies and molecular dynamic simulation studies show that the extra oxygen atom on the methionine residue can form hydrogen bonds with the glycine and aspartic acid residues of the RGD motif. These structural changes in echistatin help explain the changes in the binding characteristics of the molecule following chloramine T reaction.

【 授权许可】

Unknown