2E0N

Crystal structure of CbiL in complex with S-adenosylhomocysteine, a methyltransferase involved in anaerobic vitamin B12 biosynthesis

Summary for 2E0N

• Entry DOI: 10.2210/pdb2e0n/pdb
• Related: 2E0K
• Descriptor: Precorrin-2 C20-methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• Functional Keywords: precorrin-2, cobalt-factor ii, tetrapyrrole, s-adenosylmethionine, transferase
• Biological source: Chlorobaculum tepidum
• Total number of polymer chains: 2
• Total formula weight: 55960.04

Authors

Wada, K.,Fukuyama, K. (deposition date: 2006-10-10, release date: 2007-01-16, Last modification date: 2023-10-25)

Primary citation

Wada, K.,Harada, J.,Yaeda, Y.,Tamiaki, H.,Oh-Oka, H.,Fukuyama, K.
Crystal structures of CbiL, a methyltransferase involved in anaerobic vitamin B biosynthesis, and CbiL in complex with S-adenosylhomocysteine--implications for the reaction mechanism.
Febs J., 274:563-573, 2007

PubMed Abstract: During anaerobic cobalamin (vitamin B12) biosynthesis, CbiL catalyzes methylation at the C-20 position of a cyclic tetrapyrrole ring using S-adenosylmethionine as a methyl group source. This methylation is a key modification for the ring contraction process, by which a porphyrin-type tetrapyrrole ring is converted to a corrin ring through elimination of the modified C-20 and direct bonding of C-1 to C-19. We have determined the crystal structures of Chlorobium tepidum CbiL and CbiL in complex with S-adenosylhomocysteine (the S-demethyl form of S-adenosylmethionine). CbiL forms a dimer in the crystal, and each subunit consists of N-terminal and C-terminal domains. S-Adenosylhomocysteine binds to a cleft between the two domains, where it is specifically recognized by extensive hydrogen bonding and van der Waals interactions. The orientation of the cobalt-factor II substrate was modeled by simulation, and the predicted model suggests that the hydroxy group of Tyr226 is located in close proximity to the C-20 atom as well as the C-1 and C-19 atoms of the tetrapyrrole ring. These configurations allow us to propose a catalytic mechanism: the conserved Tyr226 residue in CbiL catalyzes the direct transfer of a methyl group from S-adenosylmethionine to the substrate through an S(N)2-like mechanism. Furthermore, the structural model of CbiL binding to its substrate suggests the axial residue coordinated to the central cobalt of cobalt-factor II.

PubMed: 17229157
DOI: 10.1111/j.1742-4658.2006.05611.x

Experimental method

X-RAY DIFFRACTION (2 Å)