title: Crystal structure of Rv2258c from Mycobacterium tuberculosis H37Rv, an S-adenosyl-l-methionine-dependent methyltransferase.
abstract: The Mycobacterium tuberculosis Rv2258c protein is an S-adenosyl-L-methionine (SAM)-dependent methyltransferase (MTase). Here, we have determined its crystal structure in three forms: a ligand-unbound form, a binary complex with sinefungin (SFG), and a binary complex with S-adenosyl-L-homocysteine (SAH). The monomer structure of Rv2258c consists of two domains which are linked by a long α-helix. The N-terminal domain is essential for dimerization and the C-terminal domain has the Class I MTase fold. Rv2258c forms a homodimer in the crystal, with the N-terminal domains facing each other. It also exists as a homodimer in solution. A DALI structural similarity search with Rv2258c reveals that the overall structure of Rv2258c is very similar to small-molecule SAM-dependent MTases. Rv2258c interacts with the bound SFG (or SAH) in an extended conformation maintained by a network of hydrogen bonds and stacking interactions. Rv2258c has a relatively large hydrophobic cavity for binding of the methyl-accepting substrate, suggesting that bulky nonpolar molecules with aromatic rings might be targeted for methylation by Rv2258c in M. tuberculosis. However, the ligand-binding specificity and the biological role of Rv2258c remain to be elucidated due to high variability of the amino acid residues defining the substrate-binding site.
authors.affiliation: Department of Biophysics and Chemical Biology, College of Natural Sciences, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Ha Na
authors.initials: HN
authors.lastname: Im
authors.affiliation: Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 08826, Republic of Korea; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Hyoun Sook
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Biophysics and Chemical Biology, College of Natural Sciences, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Doo Ri
authors.initials: DR
authors.lastname: An
authors.affiliation: Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Department of Biophysics and Chemical Biology, College of Natural Sciences, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Yoon
authors.affiliation: Department of Chemistry, College of Natural Sciences, Soongsil University, Seoul 06978, Republic of Korea.
authors.forename: Jin Kuk
authors.initials: JK
authors.lastname: Yang
authors.affiliation: Department of Biophysics and Chemical Biology, College of Natural Sciences, Seoul National University, Seoul 08826, Republic of Korea; Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: sewonsuh@snu.ac.kr.
authors.forename: Se Won
authors.initials: SW
authors.lastname: Suh
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D006867:Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008745:Methylation; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012435:S-Adenosylhomocysteine / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D008024:Ligands; D012435:S-Adenosylhomocysteine; D006867:Hydrolases; C527647:HsaD protein, Mycobacterium tuberculosis
keywords: Mycobacterium tuberculosis; Rv2258c; S-adenosyl-l-homocysteine; Sinefungin; Small-molecule methyltransferase