2X47

Crystal structure of human MACROD1

Summary for 2X47

• Entry DOI: 10.2210/pdb2x47/pdb
• Descriptor: MACRO DOMAIN-CONTAINING PROTEIN 1, SULFATE ION (3 entities in total)
• Functional Keywords: signaling protein, signal transduction, estrogen signaling
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus : Q9BQ69
• Total number of polymer chains: 1
• Total formula weight: 26552.61

Authors

Vollmar, M.,Phillips, C.,Mehrotra, P.V.,Ahel, I.,Krojer, T.,Yue, W.,Ugochukwu, E.,von Delft, F.,Bountra, C.,Arrowsmith, C.H.,Weigelt, J.,Edwards, A.,Gileadi, O. (deposition date: 2010-01-28, release date: 2010-03-02, Last modification date: 2023-12-20)

Primary citation

Chen, D.,Vollmar, M.,Rossi, M.N.,Phillips, C.,Kraehenbuehl, R.,Slade, D.,Mehrotra, P.V.,von Delft, F.,Crosthwaite, S.K.,Gileadi, O.,Denu, J.M.,Ahel, I.
Identification of Macro Domain Proteins as Novel O-Acetyl-Adp-Ribose Deacetylases.
J.Biol.Chem., 286:13261-, 2011

PubMed Abstract: Sirtuins are a family of protein lysine deacetylases, which regulate gene silencing, metabolism, life span, and chromatin structure. Sirtuins utilize NAD(+) to deacetylate proteins, yielding O-acetyl-ADP-ribose (OAADPr) as a reaction product. The macrodomain is a ubiquitous protein module known to bind ADP-ribose derivatives, which diverged through evolution to support many different protein functions and pathways. The observation that some sirtuins and macrodomains are physically linked as fusion proteins or genetically coupled through the same operon, provided a clue that their functions might be connected. Indeed, here we demonstrate that the product of the sirtuin reaction OAADPr is a substrate for several related macrodomain proteins: human MacroD1, human MacroD2, Escherichia coli YmdB, and the sirtuin-linked MacroD-like protein from Staphylococcus aureus. In addition, we show that the cell extracts derived from MacroD-deficient Neurospora crassa strain exhibit a major reduction in the ability to hydrolyze OAADPr. Our data support a novel function of macrodomains as OAADPr deacetylases and potential in vivo regulators of cellular OAADPr produced by NAD(+)-dependent deacetylation.

PubMed: 21257746
DOI: 10.1074/JBC.M110.206771

Experimental method

X-RAY DIFFRACTION (1.7 Å)