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Ligand‐induced transition in conformations of vicinal cysteine disulfides in proteins
Author(s) -
Reddy K. Kasi Amarnath,
Jayashree Muddagoni,
Govindu Panchada Ch V.,
Gowd Konkallu Hanumae
Publication year - 2021
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.26039
Subject(s) - vicinal , chemistry , cysteine , stereochemistry , ligand (biochemistry) , crystallography , receptor , biochemistry , organic chemistry , enzyme
Vicinal cysteine disulfides are thought to be associated with specific conformations of cysteine disulfides due to the restricted rotation of single bonds in an eight‐membered cyclic disulfide loop. Conformations of vicinal cysteine disulfides are analyzed using χ 1 , χ 2 , χ 3 , χ 2 ', χ 1 ' torsion angles in the crystal structures of proteins retrieved from Protein Data Bank (PDB). 85% of vicinal disulfides have (+, −)LHStaple conformation with trans configuration of the peptide bond and 9% have (−, −)RHStaple conformation with cis configured peptide bond. Conformational analysis of dipeptide Cys‐Cys vicinal disulfide by density functional theory (DFT) further supported (+, −)LHStaple, (−, −)RHStaple, and (+, +)RHStaple as the preferred conformations of vicinal disulfides. Interestingly, the rare conformations of vicinal disulfides are observed in the ligand‐bound forms of proteins and have higher disulfide strain energy. Conformations of vicinal disulfides in palmitoyl protein thioesterase 1, AChBP, and α7 nicotinic receptor are changed from preferred (+, −)LHStaple to rare (+, −)AntiLHHook/(+, −)AntiRHHook/(+, +)RHStaple conformation due to binding of ligands. Surprisingly, ligands are proximal to the vicinal disulfides in protein complexes that exhibited rare conformations of vicinal disulfides. The report has identified (+, −) LHStaple/(−, −) RHStaple as the hallmark conformations of vicinal disulfides and unraveled ligand‐induced transition in conformations of vicinal cysteine disulfides in proteins.