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The X-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with two diacid inhibitors
Auteur(s)
Erskine, Peter
Coates, Leighton
Newbold, R
Brindley, A
Stauffer, Frédéric
Wood, Stephen
Warren, Martin
Cooper, Jon
Shoolingin-Jordan, Peter
Date de parution
2001
In
Febs Letters
Vol.
2-3
No
503
De la page
196
A la page
200
Résumé
The structures of 5-aminolaevulinic acid dehydratase complexed with two irreversible inhibitors (4-oxosebacic acid and 4,7-dioxosebacic acid) have been solved at high resolution. Both inhibitors bind by forming a Schiff base link with Lys 263 at the active site. Previous inhibitor binding studies have defined the interactions made by only one of the two substrate moieties (P-side substrate) which bind to the enzyme during catalysis. The structures reported here provide an improved definition of the interactions made by both of the substrate molecules (A- and P-side substrates). The most intriguing result is the novel finding that 4,7-dioxosebacic acid forms a second Schiff base with the enzyme involving Lys 210. It has been known for many years that P-side substrate forms a Schiff base (with Lys 263) but until now there has been no evidence that binding of A-side substrate involves formation of a Schiff base with the enzyme. A catalytic mechanism involving substrate linked to the enzyme through Schiff bases at both the A- and P-sites is proposed. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
Type de publication
Resource Types::text::journal::journal article
