Crystal structure of Rv2258c from Mycobacterium tuberculosis H37Rv, an S-adenosyl-l-methionine-dependent methyltransferase

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• 作者：Ha Na Im^a ; Hyoun Sook Kim^b ; ^c ; Doo Ri An^a ; Jun Young Jang^b ; Jieun Kim^a ; Hye-Jin Yoon^b ; Jin Kuk Yang^d ; Se Won Suh^a ; ^b ; ^{sewonsuh@snu.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：MTase ; methyltransferase ; SAM ; S-adenosyl-l-methionine ; SAH ; S-adenosyl-l-homocysteine ; SFG ; sinefungin ; r.m.s. ; root mean square ; TB ; tuberculosis
• 刊名：Journal of Structural Biology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：193
• 期：3
• 页码：172-180
• 全文大小：1816 K

文摘

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.