1N2X

Crystal Structure Analysis of TM0872, a Putative SAM-dependent Methyltransferase, Complexed with SAM

Summary for 1N2X

• Entry DOI: 10.2210/pdb1n2x/pdb
• Related: 1M6Y
• Descriptor: S-adenosyl-methyltransferase mraW, SULFATE ION, S-ADENOSYLMETHIONINE, ... (4 entities in total)
• Functional Keywords: sam-dependent methyltransferase fold, protein-sam methyl donor complex, structural genomics, psi, protein structure initiative, midwest center for structural genomics, mcsg, transferase
• Biological source: Thermotoga maritima
• Cellular location: Cytoplasm (By similarity): Q9WZX6
• Total number of polymer chains: 2
• Total formula weight: 71758.95

Authors

Miller, D.J.,Anderson, W.F.,Midwest Center for Structural Genomics (MCSG) (deposition date: 2002-10-24, release date: 2003-01-28, Last modification date: 2024-11-20)

Primary citation

Miller, D.J.,Ouellette, N.,Evdokimova, E.,Savchenko, A.,Edwards, A.,Anderson, W.F.
Crystal complexes of a predicted S-adenosylmethionine-dependent methyltransferase reveal a typical AdoMet binding domain and a substrate recognition domain
Protein Sci., 12:1432-1442, 2003

PubMed Abstract: S-adenosyl-L-methionine-dependent methyltransferases (MTs) are abundant, and highly conserved across phylogeny. These enzymes use the cofactor AdoMet to methylate a wide variety of molecular targets, thereby modulating important cellular and metabolic activities. Thermotoga maritima protein 0872 (TM0872) belongs to a large sequence family of predicted MTs, ranging phylogenetically from relatively simple bacteria to humans. The genes for many of the bacterial homologs are located within operons involved in cell wall synthesis and cell division. Despite preliminary biochemical studies in E. coli and B. subtilis, the substrate specificity of this group of more than 150 proteins is unknown. As part of the Midwest Center for Structural Genomics initiative (www.mcsg.anl.gov), we have determined the structure of TM0872 in complexes with AdoMet and with S-adenosyl-L-homocysteine (AdoHcy). As predicted, TM0872 has a typical MT domain, and binds endogenous AdoMet, or co-crystallized AdoHcy, in a manner consistent with other known MT structures. In addition, TM0872 has a second domain that is novel among MTs in both its location in the sequence and its structure. The second domain likely acts in substrate recognition and binding, and there is a potential substrate-binding cleft spanning the two domains. This long and narrow cleft is lined with positively charged residues which are located opposite the S(+)-CH(3) bond, suggesting that a negatively charged molecule might be targeted for catalysis. However, AdoMet and AdoHcy are both buried, and access to the methyl group would presumably require structural rearrangement. These TM0872 crystal structures offer the first structural glimpses at this phylogenetically conserved sequence family.

PubMed: 12824489
DOI: 10.1110/ps.0302403

Experimental method

X-RAY DIFFRACTION (1.9 Å)