Cysteine Function Governs Its Conservation and Degeneration and Restricts Its Utilization on Protein Surfaces

[摘要] Cysteine (Cys) is an enigmatic ammo acid residue Although one of the least abundant, it often occurs in the functional sites of proteins Whereas free Cys is a polar amino acid, Cys in proteins is often buried, and its classification on the hydrophobicity scale is ambiguous We hypothesized that the deviation of Cys residues from the properties of a free ammo acid is due to their reactivity and addressed this possibility by examining Cys in large protein structure data sets Compared to other amino acids, Cys was characterized by the most extreme conservation pattern, with the majority of Cys being either highly conserved or poorly conserved In addition, clustering of Cys with another Cys residue was associated with high conservation, whereas exposure of Cys on protein surfaces was associated with low conservation Moreover, although clustered Cys behaved as polar residues, isolated Cys was the most buried residue of all, in disagreement with known chemical properties of Cys Thus, the anomalous hydrophobic behavior and conservation pattern of Cys can be explained by elimination of isolated Cys from protein surfaces during evolution and by clustering of other Cys residues These findings indicate that Cys abundance is governed by Cys function in proteins rather than by the sheer chemical-physical properties of free ammo acids, and suggest that a high tendency of Cys to be functionally active can considerably limit its abundance on protein surfaces (C) 2010 Elsevier Ltd All rights reserved

[发布日期] 2010-12-17

[关键词] cysteine;reactive thiols;amino acid conservation;exposure;hydrophobic scales