5GM2

Crystal structure of methyltransferase TleD complexed with SAH and teleocidin A1

5GM2 の概要

• エントリーDOI: 10.2210/pdb5gm2/pdb
• 関連するPDBエントリー: 5GM1
• 分子名称: O-methylransferase, S-ADENOSYL-L-HOMOCYSTEINE, (2S,5S)-9-[(3R)-3,7-dimethylocta-1,6-dien-3-yl]-5-(hydroxymethyl)-1-methyl-2-(propan-2-yl)-1,2,4,5,6,8-hexahydro-3H-[1,4]diazonino[7,6,5-cd]indol-3-one, ... (4 entities in total)
• 機能のキーワード: tled, teleocidin, methyltransferases, terpene cyclization, transferase
• 由来する生物種: Streptomyces blastmyceticus
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 605612.34

構造登録者

Yu, F.,Li, M.J.,Xu, C.Y.,Zhou, H.,Sun, B.,Wang, Z.J.,Xu, Q.,Xie, M.Y.,Zuo, G.,Huang, P.,Wang, Q.S.,He, J.H. (登録日: 2016-07-12, 公開日: 2016-09-28, 最終更新日: 2024-03-20)

主引用文献

Yu, F.,Li, M.J.,Xu, C.Y.,Sun, B.,Zhou, H.,Wang, Z.J.,Xu, Q.,Xie, M.Y.,Zuo, G.,Huang, P.,Guo, H.,Wang, Q.S.,He, J.H.
Crystal structure and enantioselectivity of terpene cyclization in SAM-dependent methyltransferase TleD
Biochem.J., 473:4385-4397, 2016

PubMed Abstract: TleD is a SAM (S-adenosyl-l-methionine)-dependent methyltransferase and acts as one of the key enzymes in the teleocidin B biosynthesis pathway. Besides methyl transferring, TleD also rearranges the geranyl and indole moieties of the precursor to form a six-membered ring. Moreover, it does not show homologies with any known terpenoid cyclases. In order to elucidate how such a remarkable reaction could be achieved, we determined the complex crystal structures of TleD and the cofactor analogue S-adenosyl-l-homocysteine with or without the substrate teleocidin A1. A domain-swapped pattern via an additional N-terminal α-helix is observed in TleD hexamers. Structural comparison and alignment shows that this additional N-terminal α-helix is the common feature of SAM methyltransferase-like cyclases TleD and SpnF. The residue Tyr anchors the additional N-terminal α-helix to a 'core SAM-MT fold' and is a key residue for catalytic activity. Molecular dynamics simulation results suggest that the dihedral angle C23-C24-C25-C26 of teleocidin A1 is preferred to 60-90° in the TleD and substrate complex structure, which tend to adopt a Re-face stereocenter at C25 position after reaction and is according to in vitro enzyme reaction experiments. Our results also demonstrate that methyl transfer can be a new chemical strategy for carbocation formation in the terpene cyclization, which is the key initial step.

PubMed: 27613858
DOI: 10.1042/BCJ20160695

実験手法

X-RAY DIFFRACTION (2.8 Å)