STUDIES ON THE ACTIVE-SITE OF "SUCCINYL-COA-TETRAHYDRODIPICOLINATE N-SUCCINYLTRANSFERASE - CHARACTERIZATION USING ANALOGS OF TETRAHYDRODIPICOLINATE

  • 15 May 1986
    • journal article
    • research article
    • Vol. 261  (14) , 6160-6167
Abstract
Cyclic and acyclic analogs of tetrahydrodipicolinate (THDPA) are evaluated in a study of the active site of succinyl-CoA:tetrahydrodipicolinate N-succinyltransferase. In addition to the natural substrate, THDPA, one cyclic and several acyclic compounds are also succinylated. 2-Hydroxytetrahydropyran-2,6-dicarboxylic acid is a potent competitive inhibitor having a Kis of 58 nM. Based on the results of this study, a stereochemical model for the succinylation of THDPA is proposed. The major features of this model are as follows. (1) The succinylase binds THDPA (L-configuration). (2) Hydration of the imine group follows to give 2-hydroxypiperidine-2,6-dicarboxylic acid in which the two carboxyl groups are trans. (3) Succinylation then occurs and the ring opens to give the acyclic product. It is suggested that 2-hydroxytetrahydropyran-2,6-dicarboxylic acid is a transition state analog by virtue of the fact that it structurally resembles the hydrated intermediate.