8Z54

Crystal structure of human SIRT5 in complex with succinylated Prx1 fragment

Summary for 8Z54

• Entry DOI: 10.2210/pdb8z54/pdb
• Descriptor: NAD-dependent protein deacylase sirtuin-5, mitochondrial, Peroxiredoxin-1 fragment, ZINC ION, ... (5 entities in total)
• Functional Keywords: sirt5, succinyl lysine, deacylase, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 31482.23

Authors

Yokoyama, T.,Takayama, Y. (deposition date: 2024-04-18, release date: 2024-10-09)

Primary citation

Yokoyama, T.,Takayama, Y.,Mizuguchi, M.,Nabeshima, Y.,Kusaka, K.
SIRT5 mutants reveal the role of conserved asparagine and glutamine residues in the NAD + -binding pocket.
Febs Lett., 598:2269-2280, 2024

PubMed Abstract: SIRT5, one of the mammalian sirtuins, specifically recognizes succinyl-lysine residues on proteins and catalyzes the desuccinylation reaction. In this study, we characterized SIRT5 mutants with hydrophobic amino acid substitutions at Q140 and N141, in addition to the catalytic residue H158, known as an active site residue, by the Michaelis-Menten analysis and X-ray crystallography. Kinetic analysis showed that the catalytic efficiency (k/K) of the Q140L and N141V mutants decreased to 0.02 times and 0.0038 times that of the wild-type SIRT5, respectively, with the activity of the N141V mutant becoming comparable to that of the H158M mutant. Our findings indicate that N141 contributes significantly to the desuccinylation reaction.

PubMed: 39031546
DOI: 10.1002/1873-3468.14961

Experimental method

X-RAY DIFFRACTION (1.45 Å)