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Updated: Jul 4, 2026
11:27
X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
Published on: May 13, 2020
Evolution of quaternary structure in a homotetrameric enzyme
Michael D W Griffin1, Renwick C J Dobson, F Grant Pearce
1School of Biological Sciences, University of Canterbury, Christchurch 8140, New Zealand.
Journal of Molecular Biology
|June 17, 2008
Summary
Disrupting the tetrameric structure of dihydrodipicolinate synthase (DHDPS) reduces enzyme activity. The homotetrameric structure optimizes dynamics and substrate specificity, crucial for (S)-lysine biosynthesis and antibiotic development.
Area of Science:
- Biochemistry
- Enzymology
- Structural Biology
Background:
- Dihydrodipicolinate synthase (DHDPS) is a key enzyme in (S)-lysine biosynthesis.
- DHDPS is a validated antibiotic target, typically existing as a homotetramer.
- The functional significance of the DHDPS homotetrameric structure remains incompletely understood.
Purpose of the Study:
- To investigate the role of quaternary structure in DHDPS function.
- To compare the properties of engineered dimeric DHDPS variants with the wild-type tetramer.
- To elucidate how enzyme structure influences catalytic activity and specificity.
Main Methods:
- Engineering of dimeric DHDPS variants from Escherichia coli.
- X-ray crystallography to determine enzyme structures.
- Enzyme activity assays in solution.
- Small-angle X-ray scattering (SAXS) and mutagenesis.
- B-factor analysis of crystal structures.
Main Results:
- Dimeric DHDPS variants exhibit significantly reduced enzymatic activity compared to the wild-type tetramer.
- X-ray crystallography confirmed the active site integrity in dimeric forms but revealed trapped substrate analogue adducts.
- Heating dimeric enzymes partially restored activity.
- Data suggest the tetrameric structure minimizes dynamic fluctuations and enhances substrate specificity.
Conclusions:
- The homotetrameric structure of DHDPS is critical for optimal enzyme activity and specificity.
- Quaternary structure likely evolved to control protein dynamics and prevent non-productive reactions.
- Understanding DHDPS quaternary structure offers insights into enzyme evolution and antibiotic target optimization.
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