Insight into the dimer dissociation process of the Chromobacterium violaceum (S)-selective amine transaminase
Ruggieri, Federica ; Campillo-Brocal, Jonatan C. ; Chen, Shan ; Humble, Maria S. ; Walse, Björn LU ; Logan, Derek T. LU
and Berglund, Per
(2019)
In Scientific Reports
9(1).
- Abstract
One of the main factors hampering the implementation in industry of transaminase-based processes for the synthesis of enantiopure amines is their often low storage and operational stability. Our still limited understanding of the inactivation processes undermining the stability of wild-type transaminases represents an obstacle to improving their stability through enzyme engineering. In this paper we present a model describing the inactivation process of the well-characterized (S)-selective amine transaminase from Chromobacterium violaceum. The cornerstone of the model, supported by structural, computational, mutagenesis and biophysical data, is the central role of the catalytic lysine as a conformational switch. Upon... (More)
One of the main factors hampering the implementation in industry of transaminase-based processes for the synthesis of enantiopure amines is their often low storage and operational stability. Our still limited understanding of the inactivation processes undermining the stability of wild-type transaminases represents an obstacle to improving their stability through enzyme engineering. In this paper we present a model describing the inactivation process of the well-characterized (S)-selective amine transaminase from Chromobacterium violaceum. The cornerstone of the model, supported by structural, computational, mutagenesis and biophysical data, is the central role of the catalytic lysine as a conformational switch. Upon breakage of the lysine-PLP Schiff base, the strain associated with the catalytically active lysine conformation is dissipated in a slow relaxation process capable of triggering the known structural rearrangements occurring in the holo-to-apo transition and ultimately promoting dimer dissociation. Due to the occurrence in the literature of similar PLP-dependent inactivation models valid for other non-transaminase enzymes belonging to the same fold-class, the role of the catalytic lysine as conformational switch might extend beyond the transaminase enzyme group and offer new insight to drive future non-trivial engineering strategies.
(Less)
- author
- Ruggieri, Federica
; Campillo-Brocal, Jonatan C.
; Chen, Shan
; Humble, Maria S.
; Walse, Björn
LU
; Logan, Derek T.
LU
and Berglund, Per
- publishing date
- 2019-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 9
- issue
- 1
- article number
- 16946
- pages
- 15 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:31740704
- scopus:85075113878
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-019-53177-3
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2019, The Author(s).
- id
- e37bbc54-c54d-4f33-821f-c9ab4c6e2fa1
- date added to LUP
- 2022-04-08 08:51:41
- date last changed
- 2024-06-23 03:31:42
@article{e37bbc54-c54d-4f33-821f-c9ab4c6e2fa1,
abstract = {{<p>One of the main factors hampering the implementation in industry of transaminase-based processes for the synthesis of enantiopure amines is their often low storage and operational stability. Our still limited understanding of the inactivation processes undermining the stability of wild-type transaminases represents an obstacle to improving their stability through enzyme engineering. In this paper we present a model describing the inactivation process of the well-characterized (<i>S</i>)-selective amine transaminase from <i>Chromobacterium violaceum</i>. The cornerstone of the model, supported by structural, computational, mutagenesis and biophysical data, is the central role of the catalytic lysine as a conformational switch. Upon breakage of the lysine-PLP Schiff base, the strain associated with the catalytically active lysine conformation is dissipated in a slow relaxation process capable of triggering the known structural rearrangements occurring in the holo-to-apo transition and ultimately promoting dimer dissociation. Due to the occurrence in the literature of similar PLP-dependent inactivation models valid for other non-transaminase enzymes belonging to the same fold-class, the role of the catalytic lysine as conformational switch might extend beyond the transaminase enzyme group and offer new insight to drive future non-trivial engineering strategies.</p>}},
author = {{Ruggieri, Federica and Campillo-Brocal, Jonatan C. and Chen, Shan and Humble, Maria S. and Walse, Björn and Logan, Derek T. and Berglund, Per}},
issn = {{2045-2322}},
language = {{eng}},
month = {{12}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Insight into the dimer dissociation process of the <i>Chromobacterium violaceum</i> (<i>S</i>)-selective amine transaminase}},
url = {{http://dx.doi.org/10.1038/s41598-019-53177-3}},
doi = {{10.1038/s41598-019-53177-3}},
volume = {{9}},
year = {{2019}},
}