Stacked beta-bulges in thymidylate synthase account for a novel right-handed rotation between opposing beta-sheets.

摘要: The beta-sandwich in thymidylate synthase comprises two six-stranded mixed beta-sheets, each contributed by one subunit of the dimeric molecule. In contrast to other proteins known structure which beta-sheets stack face face, central dimer are related a right-handed rather than left-handed twist. Using highly refined model an Escherichia coli ternary complex, we show that individual severely distorted unusual series stacked beta-bulges, partitions larger sheet into smaller approximately orthogonal another. These beta-bulges locally stabilized hydrogen bonding involving eight conserved residues. This extended anchors phosphate bound dUMP and controls precise orientation catalytically essential active site cysteine. Stereochemical factors associated with pronounced crease caused these bulges account for twist opposing beta-sheets.