5z46

Publication Abstract from PubMed

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.

Molecular Insight into the Mg(2+) -Dependent Allosteric Control of Indole Prenylation by Aromatic Prenyltransferase AmbP1.,Awakawa T, Mori T, Nakashima Y, Zhai R, Wong CP, Hillwig ML, Liu X, Abe I Angew Chem Int Ed Engl. 2018 Jun 4;57(23):6810-6813. doi: 10.1002/anie.201800855., Epub 2018 May 7. PMID:29677386^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.