4AO4

Structural Determinants of the beta-Selectivity of a Bacterial Aminotransferase

Summary for 4AO4

• Entry DOI: 10.2210/pdb4ao4/pdb
• Related: 2YKU 2YKV 2YKX 2YKY
• Descriptor: Beta-transaminase, (3R)-3-[({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)AMINO]-5-METHYLHEXANOIC ACID, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: transferase, aminotransferase
• Biological source: Mesorhizobium sp. LUK
• Total number of polymer chains: 3
• Total formula weight: 150403.95

Authors

Wybenga, G.G.,Crismaru, C.G.,Janssen, D.B.,Dijkstra, B.W. (deposition date: 2012-03-23, release date: 2012-06-06, Last modification date: 2024-05-08)

Primary citation

Wybenga, G.G.,Crismaru, C.G.,Janssen, D.B.,Dijkstra, B.W.
Structural determinants of the beta-selectivity of a bacterial aminotransferase.
J. Biol. Chem., 287:28495-28502, 2012

PubMed Abstract: Chiral β-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 β-Phe and derivatives thereof. Using x-ray crystallography, we solved structures of MesAT in complex with (S)-β-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 β-amino acid is located on the 3'-oxygen side of the PLP cofactor. The same binding pocket is utilized by MesAT to bind the α-carboxylate group of an α-amino acid. A β-amino acid thus binds in a reverse orientation in the active site of MesAT compared with an α-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 β- and α-amino acids.

PubMed: 22745123
DOI: 10.1074/jbc.M112.375238

Experimental method

X-RAY DIFFRACTION (1.95 Å)