5GM1

Crystal structure of methyltransferase TleD complexed with SAH

Summary for 5GM1

• Entry DOI: 10.2210/pdb5gm1/pdb
• Related: 5GM2
• Descriptor: O-methylransferase, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• Functional Keywords: tled, teleocidin, methyltransferases, terpene cyclization, transferase
• Biological source: Streptomyces blastmyceticus
• Total number of polymer chains: 18
• Total formula weight: 598119.65

Authors

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. (deposition date: 2016-07-12, release date: 2016-09-28, Last modification date: 2024-03-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.501 Å)