In reactions dependent on its co-substrate NAD, SIRT5 catalyzes the desuccinylation/demalonylation of protein acylated lysine residues and, far less efficiently, lysine deacetylation. SIRT5, like SIRTs 3 and 4, is located in the mitochondria (residues 1-36 encode a presumptive transit sequence), although some reports indicate additional localization to the cytoplasm, possibly of isoform 1 specifically. Recent proteomic studies reveal relatively widespread lysine succinylation, which, at least in the mitochondrial matrix, may result from non-enzymatic reaction of lysyl amines with succinyl-CoA. SIRT5 expression levels can be elevated by calorie restriction or fasting and metabolic regulatory functions for both SIRT5 desuccinylation and deacetylation activities have been proposed. Activation of the urea cycle enzyme carbamoyl phosphate sythetase 1 (CPS1) by SIRT5-catalyzed deacetylation and of SOD1 (superoxide dismutase 1) by SIRT5-catalyzed desuccinylation have been demonstrated. As in the case of SIRT1, SIRT5 deacetylation activity (but not desuccinylation) can be activated by certain polyphenols such as resveratrol or isoliquiritigenin, although at ~10x higher concentrations. A crystal structure of SIRT5 in complex with resveratrol and a fluorigenic acetylated peptide substrate has been obtained and is the basis of a proposed activation mechanism in which resveratrol binds to form a “top cover” over the peptide binding cleft and interacts with the peptide substrate C-terminal to the acetyllysine. However, given the absence in SIRT5 of structures homologous to the N-terminal domain that enhances SIRT1 catalytic efficiency and to the conserved, structured region and residue (E230) important for full SIRT1 activation by resveratrol and other compounds, it is still unclear to what extent this model will be applicable to SIRT1.
ACCESSION #: NM_012241
INCLUDES AMINO ACIDS: 37-310 (C-term.)
TAG(S): N-terminal His-tag
MW: 32.3 kDa
EXPRESSION SYSTEM: E. coli
SUPPLIED AS: Solution of purified recombinant protein in 50 mM Tris/HCl pH 7.5, 500 mM NaCl, 1 mM TCEP, 10% glycerol (v/v).
STORAGE: -80°C, aliquot and snap-freeze after first use.
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