4YL7

Crystal structure of the indole prenyltransferase MpnD from Marinactinospora thermotolerans

Summary for 4YL7

• Entry DOI: 10.2210/pdb4yl7/pdb
• Descriptor: Aromatic prenyltransferase (2 entities in total)
• Functional Keywords: transferase, pt-fold, indolactam v, indole prenyltransferase
• Biological source: Marinactinospora thermotolerans
• Total number of polymer chains: 1
• Total formula weight: 41027.00

Authors

Mori, T.,Morita, H.,Abe, I. (deposition date: 2015-03-05, release date: 2016-03-16, Last modification date: 2023-11-08)

Primary citation

Mori, T.,Zhang, L.,Awakawa, T.,Hoshino, S.,Okada, M.,Morita, H.,Abe, I.
Manipulation of prenylation reactions by structure-based engineering of bacterial indolactam prenyltransferases.
Nat Commun, 7:10849-10849, 2016

PubMed Abstract: Prenylation reactions play crucial roles in controlling the activities of biomolecules. Bacterial prenyltransferases, TleC from Streptomyces blastmyceticus and MpnD from Marinactinospora thermotolerans, catalyse the 'reverse' prenylation of (-)-indolactam V at the C-7 position of the indole ring with geranyl pyrophosphate or dimethylallyl pyrophosphate, to produce lyngbyatoxin or pendolmycin, respectively. Using in vitro analyses, here we show that both TleC and MpnD exhibit relaxed substrate specificities and accept various chain lengths (C5-C25) of the prenyl donors. Comparisons of the crystal structures and their ternary complexes with (-)-indolactam V and dimethylallyl S-thiophosphate revealed the intimate structural details of the enzyme-catalysed 'reverse' prenylation reactions and identified the active-site residues governing the selection of the substrates. Furthermore, structure-based enzyme engineering successfully altered the preference for the prenyl chain length of the substrates, as well as the regio- and stereo-selectivities of the prenylation reactions, to produce a series of unnatural novel indolactams.

PubMed: 26952246
DOI: 10.1038/ncomms10849

Experimental method

X-RAY DIFFRACTION (1.601 Å)