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Engineering of an intersubunit disulfide bridge in the iron-superoxide dismutase of Mycobacterium tuberculosis

Engineering of an intersubunit disulfide bridge in the iron-superoxide dismutase of Mycobacterium tuberculosis
Engineering of an intersubunit disulfide bridge in the iron-superoxide dismutase of Mycobacterium tuberculosis
With the aim of enhancing interactions involved in dimer formation, an intersubunit disulfide bridge was engineered in the superoxide dismutase enzyme of Mycobacterium tuberculosis. Ser-123 was chosen for mutation to cysteine since it resides at the dimer interface where the serine side chain interacts with the same residue in the opposite subunit. Gel electrophoresis and X-ray crystallographic studies of the expressed mutant confirmed formation of the disulfide bond under nonreducing conditions. However, the mutant protein was found to be less stable than the wild type as judged by susceptibility to denaturation in the presence of guanidine hydrochloride. Decreased stability probably results from formation of a disulfide bridge with a suboptimal torsion angle and exclusion of solvent molecules from the dimer interface.
protein engineering, X-ray crystallography, site-directed mutagenesis, superoxide dismutase
0003-9861
69-76
Bunting, K.A.
f07a3cce-4a3e-41f8-ad5d-3cd691010e2d
Cooper, J.B.
d9f0f6a8-1260-48fc-aa5c-3dbc650e3ec0
Tickle, I.J.
7d0714ba-37d0-4b7d-8680-8a4b89ea0a37
Young, D.B.
63565aac-a5a2-41e5-bfb5-2cb087079f32
Bunting, K.A.
f07a3cce-4a3e-41f8-ad5d-3cd691010e2d
Cooper, J.B.
d9f0f6a8-1260-48fc-aa5c-3dbc650e3ec0
Tickle, I.J.
7d0714ba-37d0-4b7d-8680-8a4b89ea0a37
Young, D.B.
63565aac-a5a2-41e5-bfb5-2cb087079f32

Bunting, K.A., Cooper, J.B., Tickle, I.J. and Young, D.B. (2002) Engineering of an intersubunit disulfide bridge in the iron-superoxide dismutase of Mycobacterium tuberculosis. Archives of Biochemistry and Biophysics, 397 (1), 69-76.

Record type: Article

Abstract

With the aim of enhancing interactions involved in dimer formation, an intersubunit disulfide bridge was engineered in the superoxide dismutase enzyme of Mycobacterium tuberculosis. Ser-123 was chosen for mutation to cysteine since it resides at the dimer interface where the serine side chain interacts with the same residue in the opposite subunit. Gel electrophoresis and X-ray crystallographic studies of the expressed mutant confirmed formation of the disulfide bond under nonreducing conditions. However, the mutant protein was found to be less stable than the wild type as judged by susceptibility to denaturation in the presence of guanidine hydrochloride. Decreased stability probably results from formation of a disulfide bridge with a suboptimal torsion angle and exclusion of solvent molecules from the dimer interface.

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More information

Published date: 1 January 2002
Keywords: protein engineering, X-ray crystallography, site-directed mutagenesis, superoxide dismutase

Identifiers

Local EPrints ID: 56141
URI: http://eprints.soton.ac.uk/id/eprint/56141
ISSN: 0003-9861
PURE UUID: 539c6790-4847-46b2-b6a7-7e0b7d29bf3b

Catalogue record

Date deposited: 07 Aug 2008
Last modified: 22 Jul 2022 21:06

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Contributors

Author: K.A. Bunting
Author: J.B. Cooper
Author: I.J. Tickle
Author: D.B. Young

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