3BUS

Crystal Structure of RebM

Summary for 3BUS

• Entry DOI: 10.2210/pdb3bus/pdb
• Descriptor: Methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• Functional Keywords: rebeccamycin synthesis, methyltransferase, transferase
• Biological source: Lechevalieria aerocolonigenes
• Total number of polymer chains: 2
• Total formula weight: 60349.24

Authors

McCoy, J.G.,Singh, S.,Bingman, C.A.,Thorson, J.S.,Phillips Jr., G.N. (deposition date: 2008-01-03, release date: 2008-03-25, Last modification date: 2024-10-30)

Primary citation

Singh, S.,McCoy, J.G.,Zhang, C.,Bingman, C.A.,Phillips Jr., G.N.,Thorson, J.S.
Structure and mechanism of the rebeccamycin sugar 4'-O-methyltransferase RebM.
J.Biol.Chem., 283:22628-22636, 2008

PubMed Abstract: The 2.65-angstroms crystal structure of the rebeccamycin 4'-O-methyltransferase RebM in complex with S-adenosyl-l-homocysteine revealed RebM to adopt a typical S-adenosylmethionine-binding fold of small molecule O-methyltransferases (O-MTases) and display a weak dimerization domain unique to MTases. Using this structure as a basis, the RebM substrate binding model implicated a predominance of nonspecific hydrophobic interactions consistent with the reported ability of RebM to methylate a wide range of indolocarbazole surrogates. This model also illuminated the three putative RebM catalytic residues (His140/141 and Asp166) subsequently found to be highly conserved among sequence-related natural product O-MTases from GC-rich bacteria. Interrogation of these residues via site-directed mutagenesis in RebM demonstrated His140 and Asp166 to be most important for catalysis. This study reveals RebM to be a member of the general acid/base-dependent O-MTases and, as the first crystal structure for a sugar O-MTase, may also present a template toward the future engineering of natural product MTases for combinatorial applications.

PubMed: 18502766
DOI: 10.1074/jbc.M800503200

Experimental method

X-RAY DIFFRACTION (2.65 Å)