6PGN

PagF single mutant with GPP

6PGN の概要

• エントリーDOI: 10.2210/pdb6pgn/pdb
• 分子名称: PagF, MAGNESIUM ION, GERANYL DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: geranylation, prenylation, cyanobactin, transferase
• 由来する生物種: Planktothrix agardhii
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35487.39

構造登録者

Nair, S.K.,Hao, Y.,Estrada, P. (登録日: 2019-06-24, 公開日: 2019-07-24, 最終更新日: 2023-10-11)

主引用文献

Estrada, P.,Morita, M.,Hao, Y.,Nair, S.K.,Schmidt, E.W.
A Single Amino Acid Switch Alters the Isoprene Donor Specificity in Ribosomally Synthesized and Post-Translationally Modified Peptide Prenyltransferases
J. Am. Chem. Soc., 140:8124-8127, 2018

PubMed Abstract: Mutation at a single amino acid alters the isoprene donor specificity of prenyltransferases involved in the modification of ribosomally synthesized and post-translationally modified peptides (RiPPs). Though most characterized RiPP prenyltransferases carry out the regiospecific transfer of C dimethylallyl donor to the side chain atoms on macrocyclic acceptor substrates, the elucidation of the cyanobactin natural product piricyclamide 70005E1 identifies an O-geranyl modification on Tyr, a reaction with little prior biochemical precedence. Reconstitution and kinetic studies of the presumptive geranyltransferase PirF shows that the enzyme utilizes a C donor, with no C transferase activity. The crystal structure of PirF reveals a single amino acid difference in the vicinity of the isoprene-binding pocket, relative to the C utilizing enzymes. Remarkably, only a single amino acid mutation is necessary to completely switch the donor specificity from a C to a C prenyltransferase, and vice versa. Lastly, we demonstrate that these enzymes may be used for the chemospecific attachment of C or C lipid groups on lanthipeptides, an unrelated class of RiPP natural products. These studies represent a rare example where prenyl donor specificity can be discretely altered, which expands the arsenal of synthetic biology tools for tuning biological activities of peptide natural products.

PubMed: 29924593
DOI: 10.1021/jacs.8b05187

実験手法

X-RAY DIFFRACTION (1.85 Å)