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Product inhibition in the radical S-adenosylmethionine family

Product inhibition in the radical S-adenosylmethionine family
Product inhibition in the radical S-adenosylmethionine family
Members of the radical S-adenosylmethionine (AdoMet) superfamily reductively cleave AdoMet to generate the highly reactive 5?-deoxyadenosyl radical (DOA) which initiates biological transformations by abstraction of a hydrogen atom. We demonstrate that three members of the family: biotin synthase (BioB), lipoyl synthase (LipA) and tyrosine lyase (ThiH) are inhibited in vitro by a combination of the products 5?-deoxyadenosine (DOA) and methionine. These results suggest the observed inhibition is a common feature of the radical AdoMet proteins that form DOA and methionine as products. Addition of 5?-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) to BioB, LipA or ThiH activity assays removed the product inhibition by catalysing the hydrolysis of DOA and gave an increase in activity.
iron–sulfur cluster, s-adenosylmethionine, enzyme kinetics, product inhibition
0014-5793
1358-1362
Challand, Martin R.
03bb1ded-9274-4525-8377-8e5930f30d65
Ziegert, Tillman
e5a19896-c311-49f4-92d0-1bbd289dd2d9
Douglas, Paul
a6304b96-3482-4468-9a45-bc05153ca270
Wood, Robert J.
f8754320-328e-4622-ac32-ef815fdae3b6
Kriek, Marco
c3e820c2-c59b-49c8-a792-f64a69e4401a
Shaw, Nicholas M.
659f54a9-df16-40f4-9d0a-115fdf91a5a1
Roach, Peter L.
ca94060c-4443-482b-af3e-979243488ba9
Challand, Martin R.
03bb1ded-9274-4525-8377-8e5930f30d65
Ziegert, Tillman
e5a19896-c311-49f4-92d0-1bbd289dd2d9
Douglas, Paul
a6304b96-3482-4468-9a45-bc05153ca270
Wood, Robert J.
f8754320-328e-4622-ac32-ef815fdae3b6
Kriek, Marco
c3e820c2-c59b-49c8-a792-f64a69e4401a
Shaw, Nicholas M.
659f54a9-df16-40f4-9d0a-115fdf91a5a1
Roach, Peter L.
ca94060c-4443-482b-af3e-979243488ba9

Challand, Martin R., Ziegert, Tillman, Douglas, Paul, Wood, Robert J., Kriek, Marco, Shaw, Nicholas M. and Roach, Peter L. (2009) Product inhibition in the radical S-adenosylmethionine family. FEBS Letters, 583 (8), 1358-1362. (doi:10.1016/j.febslet.2009.03.044).

Record type: Article

Abstract

Members of the radical S-adenosylmethionine (AdoMet) superfamily reductively cleave AdoMet to generate the highly reactive 5?-deoxyadenosyl radical (DOA) which initiates biological transformations by abstraction of a hydrogen atom. We demonstrate that three members of the family: biotin synthase (BioB), lipoyl synthase (LipA) and tyrosine lyase (ThiH) are inhibited in vitro by a combination of the products 5?-deoxyadenosine (DOA) and methionine. These results suggest the observed inhibition is a common feature of the radical AdoMet proteins that form DOA and methionine as products. Addition of 5?-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) to BioB, LipA or ThiH activity assays removed the product inhibition by catalysing the hydrolysis of DOA and gave an increase in activity.

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More information

Published date: 17 April 2009
Keywords: iron–sulfur cluster, s-adenosylmethionine, enzyme kinetics, product inhibition

Identifiers

Local EPrints ID: 146163
URI: http://eprints.soton.ac.uk/id/eprint/146163
ISSN: 0014-5793
PURE UUID: 21b6391b-f550-493d-8619-79a4c2e91520
ORCID for Peter L. Roach: ORCID iD orcid.org/0000-0001-9880-2877

Catalogue record

Date deposited: 21 Apr 2010 08:59
Last modified: 14 Mar 2024 00:54

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Contributors

Author: Martin R. Challand
Author: Tillman Ziegert
Author: Paul Douglas
Author: Robert J. Wood
Author: Marco Kriek
Author: Nicholas M. Shaw
Author: Peter L. Roach ORCID iD

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