2P5X

Crystal structure of Maf domain of human N-acetylserotonin O-methyltransferase-like protein

Summary for 2P5X

• Entry DOI: 10.2210/pdb2p5x/pdb
• Descriptor: N-acetylserotonin O-methyltransferase-like protein, PHOSPHATE ION (3 entities in total)
• Functional Keywords: asmtl, structural genomics, structural genomics consortium, sgc, cell cycle
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 51828.92

Authors

Min, J.,Wu, H.,Dombrovski, L.,Loppnau, P.,Weigelt, J.,Sundstrom, M.,Arrowsmith, C.H.,Edwards, A.M.,Bochkarev, A.,Plotnikov, A.N.,Structural Genomics Consortium (SGC) (deposition date: 2007-03-16, release date: 2007-03-27, Last modification date: 2023-08-30)

Primary citation

Tchigvintsev, A.,Tchigvintsev, D.,Flick, R.,Popovic, A.,Dong, A.,Xu, X.,Brown, G.,Lu, W.,Wu, H.,Cui, H.,Dombrowski, L.,Joo, J.C.,Beloglazova, N.,Min, J.,Savchenko, A.,Caudy, A.A.,Rabinowitz, J.D.,Murzin, A.G.,Yakunin, A.F.
Biochemical and structural studies of conserved maf proteins revealed nucleotide pyrophosphatases with a preference for modified nucleotides.
Chem.Biol., 20:1386-1398, 2013

PubMed Abstract: Maf (for multicopy associated filamentation) proteins represent a large family of conserved proteins implicated in cell division arrest but whose biochemical activity remains unknown. Here, we show that the prokaryotic and eukaryotic Maf proteins exhibit nucleotide pyrophosphatase activity against 5-methyl-UTP, pseudo-UTP, 5-methyl-CTP, and 7-methyl-GTP, which represent the most abundant modified bases in all organisms, as well as against canonical nucleotides dTTP, UTP, and CTP. Overexpression of the Maf protein YhdE in E. coli cells increased intracellular levels of dTMP and UMP, confirming that dTTP and UTP are the in vivo substrates of this protein. Crystal structures and site-directed mutagenesis of Maf proteins revealed the determinants of their activity and substrate specificity. Thus, pyrophosphatase activity of Maf proteins toward canonical and modified nucleotides might provide the molecular mechanism for a dual role of these proteins in cell division arrest and house cleaning.

PubMed: 24210219
DOI: 10.1016/j.chembiol.2013.09.011

Experimental method

X-RAY DIFFRACTION (2 Å)