Hypervalent Nonbonded Interactions of a Divalent Sulfur Atom. Implications in Protein Architecture and the Functions

Molecules

Michio Iwaoka¹ 

[1] Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan

关键词: Protein Data Bank;    chalcogen bonds;    σ-hole bonds;    molecular assembly;    protein engineering;    drug design;   

DOI  :  10.3390/molecules17067266

来源: mdpi

【 摘 要 】

In organic molecules a divalent sulfur atom sometimes adopts weak coordination to a proximate heteroatom (X). Such hypervalent nonbonded S···X interactions can control the molecular structure and chemical reactivity of organic molecules, as well as their assembly and packing in the solid state. In the last decade, similar hypervalent interactions have been demonstrated by statistical database analysis to be present in protein structures. In this review, weak interactions between a divalent sulfur atom and an oxygen or nitrogen atom in proteins are highlighted with several examples. S···O interactions in proteins showed obviously different structural features from those in organic molecules (i.e., π_O → σ_S* versus n_O → σ_S* directionality). The difference was ascribed to the HOMO of the amide group, which expands in the vertical direction (π_O) rather than in the plane (n_O). S···X interactions in four model proteins, phospholipase A₂ (PLA₂), ribonuclease A (RNase A), insulin, and lysozyme, have also been analyzed. The results suggested that S···X interactions would be important factors that control not only the three-dimensional structure of proteins but also their functions to some extent. Thus, S···X interactions will be useful tools for protein engineering and the ligand design.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.