Premium
Chloramine T‐induced structural and biochemical changes in echistatin
Author(s) -
Chandra Kumar C.,
Nie Huiming,
Armstrong Lydia,
Zhang Rumin,
Vijay-Kumar Senadhi,
Tsarbopoulos Anthony
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00587-0
Subject(s) - chloramine , chloramine t , chemistry , biochemistry , medicine , computational biology , chlorine , biology , organic chemistry
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 v β 3 and α IIb β 3 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 v β 3 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.