7atl

EstCE1, a hydrolase with promiscuous acyltransferase activity

spinqualitylabelsall models 7atl, resolution 2.48Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7atl is a 1 chain structure with sequence from Uncultured bacterium pCosCE1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.478Å Ligands: 1PE, EDO, PEG, PG4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q1I192_9BACT Publication Abstract from PubMed 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 (~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'. Discovery and Design of Family VIII Carboxylesterases as Highly Efficient Acyltransferases.,Muller H, Godehard SP, Palm GJ, Berndt L, Badenhorst CPS, Becker AK, Lammers M, Bornscheuer U Angew Chem Int Ed Engl. 2020 Nov 3. doi: 10.1002/anie.202014169. PMID:33140887 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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