Journal article

Evolution of quaternary structure in a homotetrameric enzyme

Michael DW Griffin, Renwick CJ Dobson, F Grant Pearce, Laurence Antonio, Andrew E Whitten, Chu K Liew, Joel P Mackay, Jill Trewhella, Geoffrey B Jameson, Matthew A Perugini, Juliet A Gerrard

JOURNAL OF MOLECULAR BIOLOGY | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD | Published : 2008

Abstract

Dihydrodipicolinate synthase (DHDPS) is an essential enzyme in (S)-lysine biosynthesis and an important antibiotic target. All X-ray crystal structures solved to date reveal a homotetrameric enzyme. In order to explore the role of this quaternary structure, dimeric variants of Escherichia coli DHDPS were engineered and their properties were compared to those of the wild-type tetrameric form. X-ray crystallography reveals that the active site is not disturbed when the quaternary structure is disrupted. However, the activity of the dimeric enzymes in solution is substantially reduced, and a tetrahedral adduct of a substrate analogue is observed to be trapped at the active site in the crystal f..

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