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 p...

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Main Authors:	Łyskowski, Andrzej, Gruber, Christian, Steinkellner, Georg, Schürmann, Martin, Schwab, Helmut, Gruber, Karl, Steiner, Kerstin
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907554/

id	pubmed-3907554
recordtype	oai_dc
spelling	pubmed-39075542014-02-04 Crystal Structure of an (R)-Selective ω-Transaminase from Aspergillus terreus Łyskowski, Andrzej Gruber, Christian Steinkellner, Georg Schürmann, Martin Schwab, Helmut Gruber, Karl Steiner, Kerstin Research Article 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. Public Library of Science 2014-01-30 /pmc/articles/PMC3907554/ /pubmed/24498081 http://dx.doi.org/10.1371/journal.pone.0087350 Text en © 2014 Łyskowski et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Łyskowski, Andrzej Gruber, Christian Steinkellner, Georg Schürmann, Martin Schwab, Helmut Gruber, Karl Steiner, Kerstin
spellingShingle	Łyskowski, Andrzej Gruber, Christian Steinkellner, Georg Schürmann, Martin Schwab, Helmut Gruber, Karl Steiner, Kerstin Crystal Structure of an (R)-Selective ω-Transaminase from Aspergillus terreus
author_facet	Łyskowski, Andrzej Gruber, Christian Steinkellner, Georg Schürmann, Martin Schwab, Helmut Gruber, Karl Steiner, Kerstin
author_sort	Łyskowski, Andrzej
title	Crystal Structure of an (R)-Selective ω-Transaminase from Aspergillus terreus
title_short	Crystal Structure of an (R)-Selective ω-Transaminase from Aspergillus terreus
title_full	Crystal Structure of an (R)-Selective ω-Transaminase from Aspergillus terreus
title_fullStr	Crystal Structure of an (R)-Selective ω-Transaminase from Aspergillus terreus
title_full_unstemmed	Crystal Structure of an (R)-Selective ω-Transaminase from Aspergillus terreus
title_sort	crystal structure of an (r)-selective ω-transaminase from aspergillus terreus
description	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.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907554/
_version_	1612053063936245760

Crystal Structure of an (R)-Selective ω-Transaminase from Aspergillus terreus

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