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The X‐ray structure of yeast 5‐aminolaevulinic acid dehydratase complexed with two diacid inhibitors
Author(s) -
Erskine P.T,
Coates L,
Newbold R,
Brindley A.A,
Stauffer F,
Wood S.P,
Warren M.J,
Cooper J.B,
Shoolingin-Jordan P.M,
Neier R
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02721-1
Subject(s) - schiff base , dehydratase , chemistry , substrate (aquarium) , stereochemistry , enzyme , active site , binding site , catalysis , biochemistry , biology , ecology
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.