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Molecular Insight into the Mg 2+ ‐Dependent Allosteric Control of Indole Prenylation by Aromatic Prenyltransferase AmbP1
Author(s) -
Awakawa Takayoshi,
Mori Takahiro,
Nakashima Yu,
Zhai Rui,
Wong Chin Piow,
Hillwig Matthew L.,
Liu Xinyu,
Abe Ikuro
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201800855
Subject(s) - prenyltransferase , allosteric regulation , chemistry , indole test , prenylation , stereochemistry , biogenesis , enzyme , biochemistry , gene
AmbP1 is a cyanobacterial aromatic prenyltransferase and a dedicated synthase for ( R )‐3‐geranyl‐3‐isocyanovinyl indolenine ( 2 ), the biogenetic precursor for hapalindole‐type alkaloids. The regioselective geranylation of cis ‐indolyl vinyl isonitrile ( 1 ) by the standalone AmbP1 to give 2 has been shown to require a magnesium ion (Mg 2+ ) to suppress the formation of cis ‐2‐geranylindolyl vinyl isonitrile ( 3 ). Here, we report high‐resolution crystal structures of AmbP1 in complex with 1 and geranyl S ‐thiodiphosphate (GSPP) in the presence and absence of a Mg 2+ effector. The comparative study of these structures revealed a unique allosteric binding site for Mg 2+ that modulates the conformation of 1 in the active site of AmbP1 for its selective geranylation. This work defines the structural basis for AmbP1 catalysis in the biogenesis of hapalindole‐type alkaloids and provides the first atomic‐level insight to the allosteric regulation of prenyltransferases.