Structural basis for allosteric, substrate-dependent stimulation of SIRT1 activity by resveratrol

Cao D, Wang M, Qiu X, Liu D, Jiang H, Yang N · Genes & Development

The crystal structure resolved three resveratrol molecules bound to SIRT1, two of them bridging the enzyme's N-terminal domain to the coumarin-tagged peptide — a physical explanation for why activation is real but substrate-dependent, and why it appears with tagged substrates in particular.

Population

Crystallised SIRT1 in complex with resveratrol and an AMC-containing peptide

Intervention

Structural determination

Comparator

None

Limitations

The co-crystallised peptide carries the very fluorescent moiety at issue, so the structure explains the assay result rather than settling whether physiological substrates behave the same way.