Impacts of noncovalent interactions involving sulfur atoms on protein stability, structure, folding, and bioactivity

Abstract

This review discusses the various types of noncovalent interactions in which sulfur atoms participate and their effects on protein stability, structure, folding and bioactivity. Current approaches and recommendations for modelling...

Structure and Substrate Specificity of S-Methyl Thiourocanate Hydratase

“…Thioethers are usually considered weak hydrogen bond acceptors. However, hydrogen bonds to sulfur can be as strong as the classical σ-type hydrogen bonds if the sulfur atom is attached to polarizable groups, such as an imidazole ring. , Alternatively, the 2′-hydroxyl of NAD + and the sulfur atom on 7 may form a chalcogen bond, in which a lone pair on the 2′ hydroxyl interacts with a σ-hole on the sulfur atom. − Although weak in the ground state ( a , Figure ), this interaction may get stronger after the positive charge of NAD + is transferred to the imidazole ring of the substrate by conjugation ( b ). An important role of this interaction in catalysis would explain why 1 is not turned over efficiently by VaS -Me-TUC.…”

Polyaspers A and B, the First Ergosterol‐Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus sp. TJ507

“…[ 16‐18 ] As a result, the reduction of keratinocyte hyperproliferation and excessive inflammation through inhibiting TNF‐ α is instrumental in the treatment of psoriasis. [ 19‐22 ] Monoclonal antibodies targeting TNF‐ α, such as etanercept, have been developed for widespread clinical treatment of autoimmune and auto‐inflammatory diseases, including rheumatoid arthritis and psoriasis. [ 23‐25 ] However, biological macromolecule drugs still have the disadvantages of high cost, low adaptability, and more susceptibility to infection after long‐term use.…”

Importance of Noncovalent Interactions Involving Sulfur Atoms in Thiopeptide Antibiotics─Glycothiohexide α and Nocathiacin I

“…Noncovalent interactions (NCIs) 23 involving sulfur atoms play crucial roles in protein structure and function by significantly contributing to protein and peptide stability, folding, binding, and chemical reactivity. 24 These interactions also modulate the conformational preferences of small molecules, including medicinally relevant compounds. 25,26 Sulfur, as a highly polarizable atom, is involved in many important interactions such as hydrogen bonding, sulfur−lone pair interactions with heteroatoms, and interactions with πsystems.…”

“…Noncovalent interactions (NCIs) involving sulfur atoms play crucial roles in protein structure and function by significantly contributing to protein and peptide stability, folding, binding, and chemical reactivity . These interactions also modulate the conformational preferences of small molecules, including medicinally relevant compounds. , Sulfur, as a highly polarizable atom, is involved in many important interactions such as hydrogen bonding, sulfur–lone pair interactions with heteroatoms, and interactions with π-systems. − Sulfur–lone pair interactions have been shown to play key roles in determining the conformations of many small molecules, potentially allowing S···X units to function as less-polar isosteres for NH···X units in drugs. ,− Although most NCIs involving sulfur are considered to be weak, their cumulative effect can be large …”