Structural Determinants of the beta-Selectivity of a Bacterial Aminotransferase

Gjalt G. Wybenga, Ciprian G. Crismaru, Dick B. Janssen, Bauke W Dijkstra

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Chiral beta-amino acids occur as constituents of various natural and synthetic compounds with potentially useful bioactivities. The pyridoxal 5'-phosphate (PLP)-dependent S-selective transaminase from Mesorhizobium sp. strain LUK (MesAT) is a fold type I aminotransferase that can be used for the preparation of enantiopure beta-Phe and derivatives thereof. Using x-ray crystallography, we solved structures of MesAT in complex with (S)-beta-Phe, (R)-3-amino-5-methylhexanoic acid, 2-oxoglutarate, and the inhibitor 2-aminooxyacetic acid, which allowed us to unveil the molecular basis of the amino acid specificity and enantioselectivity of this enzyme. The binding pocket of the side chain of a beta-amino acid is located on the 3'-oxygen side of the PLP cofactor. The same binding pocket is utilized by MesAT to bind the alpha-carboxylate group of an alpha-amino acid. A beta-amino acid thus binds in a reverse orientation in the active site of MesAT compared with an alpha-amino acid. Such a binding mode has not been reported before for any PLP-dependent aminotransferase and shows that the active site of MesAT has specifically evolved to accommodate both beta- and alpha-amino acids.

Originele taal-2English
Pagina's (van-tot)28495-28502
Aantal pagina's8
TijdschriftThe Journal of Biological Chemistry
Nummer van het tijdschrift34
StatusPublished - 17-aug.-2012

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