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Annexin A5 D226K structure and dynamics: identification of a molecular switch for the large‐scale conformational change of domain III
Author(s) -
Sopkova-De Oliveira Santos Jana,
Vincent Michel,
Tabaries Sébastien,
Chevalier Anne,
Kerbœuf Daniel,
Russo-Marie Françoise,
Lewit-Bentley Anita,
Gallay Jacques
Publication year - 2001
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(01)02285-2
Subject(s) - conformational change , molecular dynamics , chemistry , hydrogen bond , biophysics , transition (genetics) , domain (mathematical analysis) , dynamics (music) , protein structure , crystallography , stereochemistry , molecule , computational chemistry , biochemistry , physics , biology , mathematical analysis , mathematics , organic chemistry , gene , acoustics
The domain III of annexin 5 undergoes a Ca 2+ ‐ and a pH‐dependent conformational transition of large amplitude. Modeling of the transition pathway by computer simulations suggested that the interactions between D226 and T229 in the IIID–IIIE loop on the one hand and the H‐bond interactions between W187 and T224 on the other hand, are important in this process [Sopkova et al. (2000) Biochemistry 39, 14065–14074]. In agreement with the modeling, we demonstrate in this work that the D226K mutation behaves as a molecular switch of the pH‐ and Ca 2+ ‐mediated conformational transition. In contrast, the hydrogen bonds between W187 and T224 seem marginal.