Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase.
Level 5 - mechanism / opinion, no new human data
Bench and animal research without human subjects
PubMed 22076378 · doi:10.1126/science.1207861
What was done
Investigators evaluated the enzymatic activity and acyl-binding pocket of mammalian Sirt5 in vitro, used mass spectrometry to detect succinyl and malonyl modifications on mammalian proteins, and examined the effect of Sirt5 deletion on carbamoyl phosphate synthase 1 succinylation in knockout mice.
What was found
No quantitative values or kinetic constants are reported in the abstract. Sirt5 showed efficient lysine desuccinylase and demalonylase activity in vitro, mediated by Arg(105) and Tyr(102) residues in its acyl pocket. Multiple mammalian proteins were identified with succinyl or malonyl lysine modifications, and deletion of Sirt5 in mice increased succinylation of carbamoyl phosphate synthase 1.
Why it matters
This work identifies demalonylation and desuccinylation as distinct enzymatic activities of Sirt5, establishing protein lysine succinylation as a reversible posttranslational modification in mammals.
Limits
The abstract reports no numerical data, sample sizes, or effect sizes. Findings are limited to in vitro assays and knockout mice, with no human clinical or physiological data.
Cited by
- supports Sirtuins are NAD-dependent enzymes that remove acetyl, acyl, or succinyl modifications from lysine residues on proteins to regulate enzymes and mediate gene silencing.