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Publication Abstract from PubMed

Chiral amines are important building blocks for the synthesis of pharmaceutical products, fine chemicals, and agrochemicals. omega-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)-omega-transaminase from Aspergillus terreus determined by X-ray crystallography at a resolution of 1.6 A. 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 alpha-carboxylate of pyruvate or amino acids, and the small binding pocket accommodates the smaller substituent.

Crystal Structure of an (R)-Selective omega-Transaminase from Aspergillus terreus.,Lyskowski A, Gruber C, Steinkellner G, Schurmann M, Schwab H, Gruber K, Steiner K PLoS One. 2014 Jan 30;9(1):e87350. doi: 10.1371/journal.pone.0087350. eCollection, 2014 Jan 3. PMID:24498081^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.