Structural highlights
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Publication Abstract from PubMedTleD is an S-adenosyl-L-methionine dependent methyltransferase and acts as one of the key enzymes in the teleocidin B biosynthesis pathway. Besides the methyl transferring, TleD also rearranges the geranyl and indole moiety of the precursor to form a six-membered ring. Moreover, it does not show homologies to 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 substrate teleocidin A1. A domain-swapped pattern via an additional N-terminal alpha-helix is observed in TleD hexamers. The structural comparison and alignment shows this additional N-terminal alpha-helix is the common feature of SAM-MTase-like cyclases TleD and SpnF. The residue Tyr21 anchors the additional N-terminal alpha-helix to "core SAM-MT fold" and is a key residue for catalytical activity. Molecular dynamic simulation results suggest that the dihedral angle C23-C24-C25-C26 of teleocidin A1 is preferred to 60 degrees - 90 degrees 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 methyl transfer can be a new chemical strategy for carbocation formation in the terpene cyclization, which is the key initial step. Crystal Structure and Enantioselectivity of Terpene Cyclization in SAM Dependent Methyltransferase TleD.,Yu F, Li M, Xu C, Sun B, Zhou H, Wang Z, Xu Q, Xie M, Zuo G, Huang P, Guo H, Wang Q, He J Biochem J. 2016 Sep 9. pii: BCJ20160695. PMID:27613858[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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This page was last modified 16:43, 3 October 2016.