Hypervalent nonbonded interactions of a divalent sulfur atom. Implications in protein architecture and the functions.
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.
Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan. miwaoka@tokai.ac.jp
Michio
M
Iwaoka
Noriyoshi
N
Isozumi
D000818:Animals; D030562:Databases, Protein; D006801:Humans; D015394:Molecular Structure; D009930:Organic Chemicals / Q000737:chemistry; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013455:Sulfur / Q000737:chemistry*
D009930:Organic Chemicals; D011506:Proteins; D013455:Sulfur