5A3C

Crystal structure of the ADP-ribosylating sirtuin (SirTM) from Streptococcus pyogenes in complex with NAD

Summary for 5A3C

• Entry DOI: 10.2210/pdb5a3c/pdb
• Related: 5A35 5A3A 5A3B
• Descriptor: SIR2 FAMILY PROTEIN, GLYCINE, ZINC ION, ... (6 entities in total)
• Functional Keywords: transferase, adp-ribosyltransferase, metalloprotein, nad-dependent, lipoylation, regulatory enzyme, rossmann fold, zinc binding, ros defense
• Biological source: STREPTOCOCCUS PYOGENES
• Total number of polymer chains: 1
• Total formula weight: 36234.75

Authors

Rack, J.G.M.,Morra, R.,Barkauskaite, E.,Kraehenbuehl, R.,Ariza, A.,Qu, Y.,Ortmayer, M.,Leidecker, O.,Cameron, D.R.,Matic, I.,Peleg, A.Y.,Leys, D.,Traven, A.,Ahel, I. (deposition date: 2015-05-28, release date: 2015-07-29, Last modification date: 2024-05-08)

Primary citation

Rack, J.G.,Morra, R.,Barkauskaite, E.,Kraehenbuehl, R.,Ariza, A.,Qu, Y.,Ortmayer, M.,Leidecker, O.,Cameron, D.R.,Matic, I.,Peleg, A.Y.,Leys, D.,Traven, A.,Ahel, I.
Identification of a Class of Protein Adp-Ribosylating Sirtuins in Microbial Pathogens.
Mol.Cell, 59:309-, 2015

PubMed Abstract: Sirtuins are an ancient family of NAD(+)-dependent deacylases connected with the regulation of fundamental cellular processes including metabolic homeostasis and genome integrity. We show the existence of a hitherto unrecognized class of sirtuins, found predominantly in microbial pathogens. In contrast to earlier described classes, these sirtuins exhibit robust protein ADP-ribosylation activity. In our model organisms, Staphylococcus aureus and Streptococcus pyogenes, the activity is dependent on prior lipoylation of the target protein and can be reversed by a sirtuin-associated macrodomain protein. Together, our data describe a sirtuin-dependent reversible protein ADP-ribosylation system and establish a crosstalk between lipoylation and mono-ADP-ribosylation. We propose that these posttranslational modifications modulate microbial virulence by regulating the response to host-derived reactive oxygen species.

PubMed: 26166706
DOI: 10.1016/J.MOLCEL.2015.06.013

Experimental method

X-RAY DIFFRACTION (2.03 Å)