2OJP

The crystal structure of a dimeric mutant of Dihydrodipicolinate synthase from E.coli- DHDPS-L197Y

2OJP の概要

• エントリーDOI: 10.2210/pdb2ojp/pdb
• 分子名称: Dihydrodipicolinate synthase, GLYCEROL (3 entities in total)
• 機能のキーワード: dihydrodipicolinate synthase, dhdps, dimer, lysine biosynthesis, lyase
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm: P0A6L2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63214.20

構造登録者

Griffin, M.D.W.,Dobson, R.C.J.,Antonio, L.,Perugini, M.A.,Jameson, G.B.,Gerrard, J.A. (登録日: 2007-01-13, 公開日: 2008-01-01, 最終更新日: 2023-12-27)

主引用文献

Griffin, M.D.,Dobson, R.C.,Pearce, F.G.,Antonio, L.,Whitten, A.E.,Liew, C.K.,Mackay, J.P.,Trewhella, J.,Jameson, G.B.,Perugini, M.A.,Gerrard, J.A.
Evolution of quaternary structure in a homotetrameric enzyme.
J.Mol.Biol., 380:691-703, 2008

PubMed 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 form. Remarkably, heating the dimeric enzymes increases activity. We propose that the homotetrameric structure of DHDPS reduces dynamic fluctuations present in the dimeric forms and increases specificity for the first substrate, pyruvate. By restricting motion in a key catalytic motif, a competing, non-productive reaction with a substrate analogue is avoided. Small-angle X-ray scattering and mutagenesis data, together with a B-factor analysis of the crystal structures, support this hypothesis and lead to the suggestion that in at least some cases, the evolution of quaternary enzyme structures might serve to optimise the dynamic properties of the protein subunits.

PubMed: 18556019
DOI: 10.1016/j.jmb.2008.05.038

実験手法

X-RAY DIFFRACTION (1.7 Å)