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Structures of N‐termini of helices in proteins
Author(s) -
Doig Andrew J.,
Stapley Benjamin J.,
Macarthur Malcolm W.,
Thornton Janet M.
Publication year - 1997
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560060117
Subject(s) - conformational isomerism , hydrogen bond , chemistry , stereochemistry , side chain , crystallography , helix (gastropod) , protein structure , molecule , biology , biochemistry , ecology , organic chemistry , snail , polymer
We have surveyed 393 N‐termini of α‐helices and 156 N‐termini of 3 10 ‐helices in 85 high resolution, non‐homologous protein crystal structures for N‐cap side‐chain rotamer preferences, hydrogen bonding patterns, and solvent accessibilities. We find very strong rotamer preferences that are unique to N‐cap sites. The following rules are generally observed for N‐capping in α‐helices: Thr and Ser N‐cap side chains adopt the gauche— rotamer, hydrogen bond to the N3 NH and have Ψ restricted to 164 ± 8°. Asp and Asn N‐cap side chains either adopt the gauche— rotamer and hydrogen bond to the N3 NH with Ψ = 172 ± 10°, or adopt the trans rotamer and hydrogen bond to both the N2 and N3 NH groups with Ψ = 107 ± 19°. With all other N‐caps, the side chain is found in the gauche + rotamer so that the side chain does not interact unfavorably with the N‐terminus by blocking solvation and Ψ is unrestricted. An i, i + 3 hydrogen bond from N3 NH to the N‐cap backbone C=O in more likely to form at the N‐terminus when an unfavorable N‐cap is present. In the 3 10 ‐helix Asn and Asp remain favorable N‐caps as they can hydrogen bond to the N2 NH while in the trans rotamer; in contrast, Ser and Thr are disfavored as their preferred hydrogen bonding partner (N3 NH) is inaccessible. This suggests that Ser is the optimum choice of N‐cap when α‐helix formation is to be encouraged while 3 10 ‐helix formation discouraged. The strong energetic and structural preferences found for N‐caps, which differ greatly from positions within helix interiors, suggest that N‐caps should be treated explicitly in any consideration of helical structure in peptides or proteins.