7ATL

EstCE1, a hydrolase with promiscuous acyltransferase activity

This is a non-PDB format compatible entry.

Summary for 7ATL

• Entry DOI: 10.2210/pdb7atl/pdb
• Descriptor: Esterase, DI(HYDROXYETHYL)ETHER, TETRAETHYLENE GLYCOL, ... (6 entities in total)
• Functional Keywords: esterase, acyltransferase, transacylase, hydrolase
• Biological source: uncultured bacterium pCosCE1
• Total number of polymer chains: 1
• Total formula weight: 43969.40

Authors

Palm, G.J.,Lammers, M.,Berndt, L. (deposition date: 2020-10-30, release date: 2020-11-18, Last modification date: 2024-01-31)

Primary citation

Muller, H.,Godehard, S.P.,Palm, G.J.,Berndt, L.,Badenhorst, C.P.S.,Becker, A.K.,Lammers, M.,Bornscheuer, U.T.
Discovery and Design of Family VIII Carboxylesterases as Highly Efficient Acyltransferases.
Angew.Chem.Int.Ed.Engl., 60:2013-2017, 2021

PubMed Abstract: Promiscuous acyltransferase activity is the ability of certain hydrolases to preferentially catalyze acyl transfer over hydrolysis, even in bulk water. However, poor enantioselectivity, low transfer efficiency, significant product hydrolysis, and limited substrate scope represent considerable drawbacks for their application. By activity-based screening of several hydrolases, we identified the family VIII carboxylesterase, EstCE1, as an unprecedentedly efficient acyltransferase. EstCE1 catalyzes the irreversible amidation and carbamoylation of amines in water, which enabled the synthesis of the drug moclobemide from methyl 4-chlorobenzoate and 4-(2-aminoethyl)morpholine (ca. 20 % conversion). We solved the crystal structure of EstCE1 and detailed structure-function analysis revealed a three-amino acid motif important for promiscuous acyltransferase activity. Introducing this motif into an esterase without acetyltransferase activity transformed a "hydrolase" into an "acyltransferase".

PubMed: 33140887
DOI: 10.1002/anie.202014169

Experimental method

X-RAY DIFFRACTION (2.478 Å)