8HD2

Crystal structure of SAM dependent methyltransferase encoded in type II fatty acid biosynthesis gene cluster from ladderane lipid producing anammox bacteria

Summary for 8HD2

• Entry DOI: 10.2210/pdb8hd2/pdb
• Descriptor: Methyltransf_25 domain-containing protein, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• Functional Keywords: anammox, fatty acid synthesis, ladderane lipid, sam dependent methyltransferase, biosynthetic protein
• Biological source: Candidatus Brocadia fulgida
• Total number of polymer chains: 1
• Total formula weight: 41592.39

Authors

Uegaki, T.,Nagano, S.,Hino, T. (deposition date: 2022-11-03, release date: 2023-05-17, Last modification date: 2024-05-29)

Primary citation

Uegaki, T.,Takei, T.,Yamaguchi, S.,Fujiyama, K.,Sato, Y.,Hino, T.,Nagano, S.
Anammox Bacterial S -Adenosyl-l-Methionine Dependent Methyltransferase Crystal Structure and Its Interaction with Acyl Carrier Proteins.
Int J Mol Sci, 24:-, 2023

PubMed Abstract: Ladderane lipids (found in the membranes of anaerobic ammonium-oxidizing [anammox] bacteria) have unique ladder-like hydrophobic groups, and their highly strained exotic structure has attracted the attention of scientists. Although enzymes encoded in type II fatty acid biosynthesis (FASII) gene clusters in anammox bacteria, such as -adenosyl-l-methionine (SAM)-dependent enzymes, have been proposed to construct a ladder-like structure using a substrate connected to acyl carrier protein from anammox bacteria (AmxACP), no experimental evidence to support this hypothesis was reported to date. Here, we report the crystal structure of a SAM-dependent methyltransferase from anammox bacteria (AmxMT1) that has a substrate and active site pocket between a class I SAM methyltransferase-like core domain and an additional α-helix inserted into the core domain. Structural comparisons with homologous SAM-dependent -methyltransferases in polyketide synthase, AmxACP pull-down assays, AmxACP/AmxMT1 complex structure predictions by AlphaFold, and a substrate docking simulation suggested that a small compound connected to AmxACP could be inserted into the pocket of AmxMT1, and then the enzyme transfers a methyl group from SAM to the substrate to produce branched lipids. Although the enzymes responsible for constructing the ladder-like structure remain unknown, our study, for the first time, supports the hypothesis that biosynthetic intermediates connected to AmxACP are processed by SAM-dependent enzymes, which are not typically involved in the FASII system, to produce the ladder-like structure of ladderane lipids in anammox bacteria.

PubMed: 36614187
DOI: 10.3390/ijms24010744

Experimental method

X-RAY DIFFRACTION (1.6 Å)