Crystal structures of BchU, a methyltransferase involved in bacteriochlorophyll c biosynthesis, and its complex with S-adenosylhomocysteine: implications for reaction mechanism

J Mol Biol. 2006 Jul 21;360(4):839-49. doi: 10.1016/j.jmb.2006.05.057. Epub 2006 Jun 8.

Abstract

BchU plays a role in bacteriochlorophyll c biosynthesis by catalyzing methylation at the C-20 position of cyclic tetrapyrrole chlorin using S-adenosylmethionine (SAM) as a methyl source. This methylation causes red-shifts of the electronic absorption spectrum of the light-harvesting pigment, allowing green photosynthetic bacteria to adapt to low-light environments. We have determined the crystal structures of BchU and its complex with S-adenosylhomocysteine (SAH). BchU forms a dimer and each subunit consists of two domains, an N-terminal domain and a C-terminal domain. Dimerization occurs through interactions between the N-terminal domains and the residues responsible for the catalytic reaction are in the C-terminal domain. The binding site of SAH is located in a large cavity between the two domains, where SAH is specifically recognized by many hydrogen bonds and a salt-bridge. The electron density map of BchU in complex with an analog of bacteriochlorophyll c located its central metal near the SAH-binding site, but the tetrapyrrole ring was invisible, suggesting that binding of the ring to BchU is loose and/or occupancy of the ring is low. It is likely that His290 acts as a ligand for the central metal of the substrate. The orientation of the substrate was predicted by simulation, and allows us to propose a mechanism for the BchU directed methylation: the strictly conserved Tyr246 residue acts catalytically in the direct transfer of the methyl group from SAM to the substrate through an S(N)2-like mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / biosynthesis*
  • Bacterial Proteins / chemistry
  • Bacteriochlorophylls / biosynthesis*
  • Bacteriochlorophylls / chemistry
  • Binding Sites
  • Chlorobium / enzymology*
  • Crystallography, X-Ray
  • Methylation
  • Methyltransferases / chemistry*
  • Methyltransferases / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • S-Adenosylhomocysteine / metabolism*
  • S-Adenosylmethionine / metabolism
  • Sequence Alignment
  • Substrate Specificity
  • Tetrapyrroles / chemistry
  • Zinc / metabolism

Substances

  • Bacterial Proteins
  • Bacteriochlorophylls
  • Tetrapyrroles
  • bacteriochlorophyll c
  • S-Adenosylmethionine
  • S-Adenosylhomocysteine
  • Methyltransferases
  • Zinc

Associated data

  • PDB/1X19
  • PDB/1X1A
  • PDB/1X1B
  • PDB/1X1C
  • PDB/1X1D