ISDA: 4PA8

Deposition Date 2014-04-07

Release Date 2015-04-01

Last Version Date 2025-10-01

Entry Detail

PDB ID:

4PA8

Keywords:

HYDROLASE

Title:

Crystal structure of a de novo retro-aldolase catalyzing asymmetric Michael additions, with a covalently bound product analog

Biological Source:

Source Organism(s):

Sulfolobus solfataricus (Taxon ID: 2287)

Expression System(s):

Escherichia coli

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

1.20 Å

R-Value Free:

0.17

R-Value Work:

0.13

R-Value Observed:

Space Group:

P 21 21 21

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Macromolecular Entities

Polymer Type:polypeptide(L)
Molecule:retro-aldolase
Chain IDs:A
Chain Length:258
Number of Molecules:1
Biological Source:Sulfolobus solfataricus

Ligand Molecules

2K6

GOL

SO4

Primary Citation

A Promiscuous De Novo Retro-Aldolase Catalyzes Asymmetric Michael Additions via Schiff Base Intermediates.

Garrabou, X, Beck, T, Hilvert, D.Show

Angew. Chem. Int. Ed. Engl. 54 5609 5612 (2015)

PMID: 25777153 DOI: 10.1002/anie.201500217

Abstact

Recent advances in computational design have enabled the development of primitive enzymes for a range of mechanistically distinct reactions. Here we show that the rudimentary active sites of these catalysts can give rise to useful chemical promiscuity. Specifically, RA95.5-8, designed and evolved as a retro-aldolase, also promotes asymmetric Michael additions of carbanions to unsaturated ketones with high rates and selectivities. The reactions proceed by amine catalysis, as indicated by mutagenesis and X-ray data. The inherent flexibility and tunability of this catalyst should make it a versatile platform for further optimization and/or mechanistic diversification by directed evolution.

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Primary Citation of related structures

Abstact

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