Premium
Crystal structures of CbiL, a methyltransferase involved in anaerobic vitamin B 12 biosynthesis, and CbiL in complex with S ‐adenosylhomocysteine − implications for the reaction mechanism
Author(s) -
Wada Kei,
Harada Jiro,
Yaeda Yuki,
Tamiaki Hitoshi,
Ohoka Hirozo,
Fukuyama Keiichi
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05611.x
Subject(s) - tetrapyrrole , corrin , stereochemistry , chemistry , methyl group , crystal structure , dimer , crystallography , ring (chemistry) , biochemistry , enzyme , organic chemistry , alkyl
During anaerobic cobalamin (vitamin B 12 ) 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.