5GM2
Crystal structure of methyltransferase TleD complexed with SAH and teleocidin A1
Summary for 5GM2
| Entry DOI | 10.2210/pdb5gm2/pdb |
| Related | 5GM1 |
| Descriptor | 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) |
| Functional Keywords | tled, teleocidin, methyltransferases, terpene cyclization, transferase |
| Biological source | Streptomyces blastmyceticus |
| Total number of polymer chains | 18 |
| Total formula weight | 605612.34 |
| Authors | |
| 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 Cited by 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: 27613858DOI: 10.1042/BCJ20160695 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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