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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907554/ https://www.ncbi.nlm.nih.gov/pubmed/24498081 http://dx.doi.org/10.1371/journal.pone.0087350 |
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author | Łyskowski, Andrzej Gruber, Christian Steinkellner, Georg Schürmann, Martin Schwab, Helmut Gruber, Karl Steiner, Kerstin |
author_facet | Łyskowski, Andrzej Gruber, Christian Steinkellner, Georg Schürmann, Martin Schwab, Helmut Gruber, Karl Steiner, Kerstin |
author_sort | Łyskowski, Andrzej |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3907554 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 PLoS One 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. |
spellingShingle | Research Article 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 |
title | Crystal Structure of an (R)-Selective ω-Transaminase from Aspergillus terreus
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title_full | Crystal Structure of an (R)-Selective ω-Transaminase from Aspergillus terreus
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title_fullStr | Crystal Structure of an (R)-Selective ω-Transaminase from Aspergillus terreus
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title_full_unstemmed | Crystal Structure of an (R)-Selective ω-Transaminase from Aspergillus terreus
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title_short | Crystal Structure of an (R)-Selective ω-Transaminase from Aspergillus terreus
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title_sort | crystal structure of an (r)-selective ω-transaminase from aspergillus terreus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907554/ https://www.ncbi.nlm.nih.gov/pubmed/24498081 http://dx.doi.org/10.1371/journal.pone.0087350 |
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