Crystal structure of an (R)-selective ω-transaminase from Aspergillus terreus.
Chiral amines are important building blocks for the synthesis of pharmaceutical products, fine chemicals, and agrochemicals. ω-Transaminases are able to directly synthesize enantiopure chiral amines by catalysing the transfer of an amino group from a primary amino donor to a carbonyl acceptor with pyridoxal 5'-phosphate (PLP) as cofactor. In nature, (S)-selective amine transaminases are more abundant than the (R)-selective enzymes, and therefore more information concerning their structures is available. Here, we present the crystal structure of an (R)-ω-transaminase from Aspergillus terreus determined by X-ray crystallography at a resolution of 1.6 Å. The structure of the protein is a homodimer that displays the typical class IV fold of PLP-dependent aminotransferases. The PLP-cofactor observed in the structure is present in two states (i) covalently bound to the active site lysine (the internal aldimine form) and (ii) as substrate/product adduct (the external aldimine form) and free lysine. Docking studies revealed that (R)-transaminases follow a dual binding mode, in which the large binding pocket can harbour the bulky substituent of the amine or ketone substrate and the α-carboxylate of pyruvate or amino acids, and the small binding pocket accommodates the smaller substituent.
ACIB GmbH, c/o TU Graz, Graz, Austria.
Andrzej
A
Łyskowski
ACIB GmbH, c/o TU Graz, Graz, Austria.
Christian
C
Gruber
ACIB GmbH, c/o TU Graz, Graz, Austria.
Georg
G
Steinkellner
DSM, Innovative Synthesis, Geleen, The Netherlands.
Martin
M
Schürmann
ACIB GmbH, c/o TU Graz, Graz, Austria ; Institute of Molecular Biotechnology, TU Graz, Graz, Austria.
Helmut
H
Schwab
ACIB GmbH, c/o TU Graz, Graz, Austria ; Institute of Molecular Biosciences, University of Graz, Graz, Austria.
Karl
K
Gruber
ACIB GmbH, c/o TU Graz, Graz, Austria.
Kerstin
K
Steiner
D000588:Amines / Q000737:chemistry / Q000378:metabolism; D001230:Aspergillus / Q000378:metabolism*; D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray / Q000379:methods; D007659:Ketones / Q000737:chemistry / Q000378:metabolism; D019289:Pyruvic Acid / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D000637:Transaminases / Q000737:chemistry* / Q000378:metabolism*
D000588:Amines; D007659:Ketones; D019289:Pyruvic Acid; D000637:Transaminases