Structure of the Imine Reductase from Ajellomyces dermatitidis in Three Crystal Forms

Mahima Sharma; Adam Williams; Daniel Gonzalez-Martinez; Anibal Cuetos; Gideon James Grogan

doi:10.1107/S2053230X23006672

Structure of the Imine Reductase from Ajellomyces dermatitidis in Three Crystal Forms

Mahima Sharma, Adam Williams, Daniel Gonzalez-Martinez, Anibal Cuetos, Gideon James Grogan

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

The NADPH-Dependent Imine Reductase from Ajellomyces dermatitidis (AdRedAm) catalyzes the reductive amination of certain ketones with amine donors, supplied in an equimolar ratio. We have determined the structure of AdRedAm in three forms. The first, in space group P3121, refined to 2.01 Å resolution, features two molecules (one dimer) in the asymmetric unit (asu), in complex with the redox inactive cofactor NADPH4. The second, in space group C21 and refined to 1.73 Å, has nine molecules (four and a half dimers) in the asu, each with NADP+. The third, space group P3121 and refined to 1.52 Å, had one molecule (one half-dimer) in the asu. The third structure was again in complex with NADP+ but also with the substrate 2,2-difluoroacetophenone. The different datasets permit analysis of AdRedAm in different conformational states and also reveal the molecular basis of stereoselectivity in the transformation of fluorinated acetophenone substrates by the enzyme.

Original language	English
Number of pages	7
Journal	Acta Crystallographica Section F: Structural Biology Communications
Early online date	31 Jul 2023
DOIs	https://doi.org/10.1107/S2053230X23006672
Publication status	E-pub ahead of print - 31 Jul 2023

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10.1107/S2053230X23006672Licence: CC BY

Structure of the imine reductase from Ajellomyces dermatitidis in three crystal formsFinal published version, 976 KBLicence: CC BY

X-ray Diffraction Equipment for Macromolecular Crystallography at York
Davies, G. J. (Principal investigator), Antson, A. A. (Co-investigator), Brzozowski, A. M. (Co-investigator), Cowtan, K. (Co-investigator), Fascione, M. A. (Co-investigator), Grogan, G. J. (Co-investigator), Plevin, M. J. (Co-investigator), Thomas, G. H. (Co-investigator), Wilkinson, A. J. (Co-investigator), Willems, L. I. (Co-investigator) & Wilson, K. S. (Co-investigator)
BBSRC (BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL)
18/09/20 → 17/09/22
Project: Research project (funded) › Research

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title = "Structure of the Imine Reductase from Ajellomyces dermatitidis in Three Crystal Forms",

abstract = "The NADPH-Dependent Imine Reductase from Ajellomyces dermatitidis (AdRedAm) catalyzes the reductive amination of certain ketones with amine donors, supplied in an equimolar ratio. We have determined the structure of AdRedAm in three forms. The first, in space group P3121, refined to 2.01 {\AA} resolution, features two molecules (one dimer) in the asymmetric unit (asu), in complex with the redox inactive cofactor NADPH4. The second, in space group C21 and refined to 1.73 {\AA}, has nine molecules (four and a half dimers) in the asu, each with NADP+. The third, space group P3121 and refined to 1.52 {\AA}, had one molecule (one half-dimer) in the asu. The third structure was again in complex with NADP+ but also with the substrate 2,2-difluoroacetophenone. The different datasets permit analysis of AdRedAm in different conformational states and also reveal the molecular basis of stereoselectivity in the transformation of fluorinated acetophenone substrates by the enzyme.",

author = "Mahima Sharma and Adam Williams and Daniel Gonzalez-Martinez and Anibal Cuetos and Grogan, {Gideon James}",

year = "2023",

month = jul,

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doi = "10.1107/S2053230X23006672",

language = "English",

journal = "Acta Crystallographica Section F: Structural Biology Communications",

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T1 - Structure of the Imine Reductase from Ajellomyces dermatitidis in Three Crystal Forms

AU - Sharma, Mahima

AU - Williams, Adam

AU - Gonzalez-Martinez, Daniel

AU - Cuetos, Anibal

AU - Grogan, Gideon James

PY - 2023/7/31

Y1 - 2023/7/31

N2 - The NADPH-Dependent Imine Reductase from Ajellomyces dermatitidis (AdRedAm) catalyzes the reductive amination of certain ketones with amine donors, supplied in an equimolar ratio. We have determined the structure of AdRedAm in three forms. The first, in space group P3121, refined to 2.01 Å resolution, features two molecules (one dimer) in the asymmetric unit (asu), in complex with the redox inactive cofactor NADPH4. The second, in space group C21 and refined to 1.73 Å, has nine molecules (four and a half dimers) in the asu, each with NADP+. The third, space group P3121 and refined to 1.52 Å, had one molecule (one half-dimer) in the asu. The third structure was again in complex with NADP+ but also with the substrate 2,2-difluoroacetophenone. The different datasets permit analysis of AdRedAm in different conformational states and also reveal the molecular basis of stereoselectivity in the transformation of fluorinated acetophenone substrates by the enzyme.

AB - The NADPH-Dependent Imine Reductase from Ajellomyces dermatitidis (AdRedAm) catalyzes the reductive amination of certain ketones with amine donors, supplied in an equimolar ratio. We have determined the structure of AdRedAm in three forms. The first, in space group P3121, refined to 2.01 Å resolution, features two molecules (one dimer) in the asymmetric unit (asu), in complex with the redox inactive cofactor NADPH4. The second, in space group C21 and refined to 1.73 Å, has nine molecules (four and a half dimers) in the asu, each with NADP+. The third, space group P3121 and refined to 1.52 Å, had one molecule (one half-dimer) in the asu. The third structure was again in complex with NADP+ but also with the substrate 2,2-difluoroacetophenone. The different datasets permit analysis of AdRedAm in different conformational states and also reveal the molecular basis of stereoselectivity in the transformation of fluorinated acetophenone substrates by the enzyme.

U2 - 10.1107/S2053230X23006672

DO - 10.1107/S2053230X23006672

M3 - Article

SN - 2053-230X

JO - Acta Crystallographica Section F: Structural Biology Communications

JF - Acta Crystallographica Section F: Structural Biology Communications

ER -

Structure of the Imine Reductase from Ajellomyces dermatitidis in Three Crystal Forms

Abstract

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X-ray Diffraction Equipment for Macromolecular Crystallography at York

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