PDBsum entry 5f8c

Transferase

PDB id: 5f8c

Contents

Protein chains

354 a.a.

Ligands

GOL ×4

Waters ×719

References listed in PDB file

Key reference

• Title: Crystal structure of rv2258c from mycobacterium tuberculosis h37rv, An s-Adenosyl-L-Methionine-Dependent methyltransferase.
• Authors: H.N.Im, H.S.Kim, D.R.An, J.Y.Jang, J.Kim, H.J.Yoon, J.K.Yang, S.W.Suh.
• Ref.: J Struct Biol, 2016, 193, 172-180. [DOI no: 10.1016/j.jsb.2016.01.002]
• PubMed id: 26772148

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.