Broad Analysis of Vicinal Disulfides: Occurrences, Conformations with Cis or with Trans Peptides, and Functional Roles Including Sugar Binding

• The vicinal SS bond plays highly varied functional roles but lacks an overall study.
• Despite earlier claims, protein vicinal SS can use either cis- or trans-peptide forms.
• Four reliably valid conformations are seen, which do not interconvert dynamically.
• Functions include rigidity, mobility, or binding specificity, a few with redox change.
• Broad, validated analysis clarifies conformations, changes, and a new sugar-binding role.

Vicinal disulfides between sequence-adjacent cysteine residues are very rare and rather startling structural features which play a variety of functional roles. Typically discussed as an isolated curiosity, they have never received a general treatment covering both cis and trans forms. Enabled by the growing database of high-resolution structures, required deposition of diffraction data, and improved methods for discriminating reliable from dubious cases, we identify and describe distinct protein families with reliably genuine examples of cis or trans vicinal disulfides and discuss their conformations, conservation, and functions. No cis-trans interconversions and only one case of catalytic redox function are seen. Some vicinal disulfides are essential to large, functionally coupled motions, whereas most form the centers of tightly packed internal regions. Their most widespread biological role is providing a rigid hydrophobic contact surface under the undecorated side of a sugar or multiring ligand, contributing an important aspect of binding specificity.

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