Mercury trithiolate binding (HgS3) to a de novo designed cyclic decapeptide with three preoriented cysteine side chains.
Hg2+ is an unphysiol. soft ion with high binding affinity for thiolate ligands. Its toxicity lies in the interactions with low-mol.-wt. thiols including glutathione and cysteine-contg. proteins that disrupt the thiol balance and alter vital functions. However, Hg2+ can also be detoxified via interactions with Hg2+-responsive regulatory proteins such as MerR, which coordinates Hg2+ with 3 Cys residues in a trigonal planar fashion (HgS3 coordination). Model cyclodecapeptide P3C [c(GCTCSGCSRP)] was designed to promote Hg2+ chelation in a HgS3 coordination environment through the parallel orientation of 3 Cys side-chains. The binding motif was derived from dicysteine P2C cyclodecapeptide validated previously as a model for d10 metal transporters contg. the binding sequence CxxC. Here, the formation of the mononuclear HgP3C complex with HgS3 coordination was demonstrated using electrospray-ionization mass spectrometry, UV absorption, and 199Hg NMR. Hg LIII-edge extended x-ray absorption fine structure (EXAFS) spectroscopy indicated that the Hg2+ coordination environment was T-shaped with 2 short Hg-S distances at 2.45 {\AA} and one longer distance at 2.60 {\AA}. The soln. structure of the Hg-P3C complex was refined based on 1H-1H NMR constraints and EXAFS results. The cyclic peptide scaffold had a rectangular shape with the 3 binding Cys side-chains pointing toward Hg2+. The Hg-P3CH complex had a pKa of 4.3, indicating that the HgS3 coordination mode was stable over a large range of pH values. This low pKa value suggested that the preorientation of the 3 Cys groups is particularly well-achieved for Hg2+ trithiolate coordination in P3C. [on SciFinder(R)]
Références
- Titre
- Mercury trithiolate binding (HgS3) to a de novo designed cyclic decapeptide with three preoriented cysteine side chains.
- Type de publication
- Article de revue
- Année de publication
- 2018
- Auteurs
- Sénèque, Olivier, Rousselot-Pailley Pierre, Pujol Anaïs, Boturyn Didier, Crouzy Serge, Proux Olivier, Manceau Alain, Lebrun Colette, and Delangle Pascale.
- Revue
- Inorg. Chem.
- Volume
- 57
- Pagination
- 2705–2713
- ISSN
- 0020-1669
Soumis le 5 avril 2019