Structural studies of hydroxycitrates and their relevance to certain enzymatic mechanisms

William C. Stallings, John F. Blount, Paul A. Srere, Jenny P. Glusker

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The crystal structures of the ethylenediamine salts of two diastereoisomeric hydroxycitratesy are described, and their conformations in the solid state are analyzed. In both structures, the HOCCOH torsion angle is approximately 60 ° as found for many tartrates and mesotartrates. The presence of three carboxyl groups and two hydroxyl groups in hydroxycitrates leads to 10 possible types of tridentate metal chelates. Since bacterial citrate lyase and ATP citrate lyase require metal ions, the possible geometries of hydroxycitrate chelation have been compared with those of citrate, and as a result, some information on the geometry of each enzymic active site has been obtained. If the hydroxycitrate binds in the same manner as citrate, the C(3)&z.sbnd;C(4) bond will be in the correct position to be cleaved. Other modes of binding of hydroxycitrate, if they can be accommodated in the active site of the enzyme, are nonproductive and compete with the citrate-like mode causing inhibition. It is possible, in these alternate modes of binding of hydroxycitrates, for additional binding to side chains in the active site of the enzyme to occur, resulting in extremely potent inhibition.

Original languageEnglish
Pages (from-to)431-448
Number of pages18
JournalArchives of Biochemistry and Biophysics
Volume193
Issue number2
DOIs
Publication statusPublished - Apr 1 1979

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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