5KCY

Crystal structure of the aromatic prenyltransferase AtaPT from Aspergillus terreus A8-4 in complex with geranyl S-thiolodiphosphate and (+)-butyrolactone II

Summary for 5KCY

• Entry DOI: 10.2210/pdb5kcy/pdb
• Related: 5KCG 5KCL 5KCQ 5KD0 5KD6 5KDA
• Descriptor: aromatic prenyltransferase, methyl (2~{R})-3-(4-hydroxyphenyl)-2-[(4-hydroxyphenyl)methyl]-4-oxidanyl-5-oxidanylidene-furan-2-carboxylate, GERANYL S-THIOLODIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: substrate promiscuity, abba fold, transferase
• Biological source: Aspergillus terreus
• Total number of polymer chains: 2
• Total formula weight: 95164.74

Authors

Sun, F.,Gao, B. (deposition date: 2016-06-07, release date: 2016-12-21, Last modification date: 2024-03-20)

Primary citation

Chen, R.,Gao, B.,Liu, X.,Ruan, F.,Zhang, Y.,Lou, J.,Feng, K.,Wunsch, C.,Li, S.M.,Dai, J.,Sun, F.
Molecular insights into the enzyme promiscuity of an aromatic prenyltransferase.
Nat. Chem. Biol., 13:226-234, 2017

PubMed Abstract: Aromatic prenyltransferases (aPTases) transfer prenyl moieties from isoprenoid donors to various aromatic acceptors, some of which have the rare property of extreme enzymatic promiscuity toward both a variety of prenyl donors and a large diversity of acceptors. In this study, we discovered a new aPTase, AtaPT, from Aspergillus terreus that exhibits unprecedented promiscuity toward diverse aromatic acceptors and prenyl donors and also yields products with a range of prenylation patterns. Systematic crystallographic studies revealed various discrete conformations for ligand binding with donor-dependent acceptor specificity and multiple binding sites within a spacious hydrophobic substrate-binding pocket. Further structure-guided mutagenesis of active sites at the substrate-binding pocket is responsible for altering the specificity and promiscuity toward substrates and the diversity of product prenylations. Our study reveals the molecular mechanism underlying the promiscuity of AtaPT and suggests an efficient protein engineering strategy to generate new prenylated derivatives in drug discovery applications.

PubMed: 27992881
DOI: 10.1038/nchembio.2263

Experimental method

X-RAY DIFFRACTION (2.3 Å)