PDBsum entry 5kcl

Transferase

PDB id: 5kcl

Contents

Protein chains

398 a.a.

Ligands

DST ×2

Waters ×215

PDB id:

5kcl

Name:

Transferase

Title:

Crystal structure of the aromatic prenyltransferase atapt from aspergillus terreus a8-4 in complex with dimethylallyl s- thiolodiphosphate

Structure:

Aromatic prenyltransferase. Chain: a, b. Engineered: yes. Other_details: dimethylallyl s-thiolodiphosphate

Source:

Aspergillus terreus. Organism_taxid: 33178. Strain: a8-4. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.10Å R-factor: 0.196 R-free: 0.233

Authors:

F.Sun,B.Gao

Key ref:

R.Chen et al. (2017). Molecular insights into the enzyme promiscuity of an aromatic prenyltransferase. Nat Chem Biol, 13, 226-234. PubMed id: 27992881 DOI: 10.1038/nchembio.2263

Date:

06-Jun-16 Release date: 21-Dec-16

Protein chains

A0A1B0UHJ4  (A0A1B0UHJ4_ASPTE) -  Aromatic prenyltransferase from Aspergillus terreus

Seq: 424 a.a.

Struc: 398 a.a.

DOI no: 10.1038/nchembio.2263

Nat Chem Biol 13:226-234 (2017)

PubMed id: 27992881

Molecular insights into the enzyme promiscuity of an aromatic prenyltransferase.

R.Chen, B.Gao, X.Liu, F.Ruan, Y.Zhang, J.Lou, K.Feng, C.Wunsch, S.M.Li, J.Dai, F.Sun.

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.