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Published on: March 11, 2020
Intersubunit signaling in glutamate-1-semialdehyde-aminomutase
J Stetefeld1, M Jenny, P Burkhard
1Department of Structural Biology and M. E. Müller Institute for Structural Biology, Biozentrum Universität Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland. joerg.stetefeld@unibas.ch
Summary
This study reveals how glutamate-1-semialdehyde aminomutase controls chlorophyll synthesis. A dynamic "gating loop" movement and intersubunit communication regulate enzyme activity through a molecular switch mechanism.
Area of Science:
- Biochemistry
- Enzymology
- Photosynthesis research
Background:
- Enzymes are dynamic biological catalysts.
- Allosteric communication mechanisms in enzyme catalysis remain incompletely understood.
- Glutamate-1-semialdehyde aminomutase is crucial for chlorophyll biosynthesis.
Purpose of the Study:
- To investigate the poorly understood allosteric communication linked to catalytic turnover in enzymes.
- To trap and analyze catalytic intermediates of glutamate-1-semialdehyde aminomutase.
- To elucidate the atomic-level mechanisms of intersubunit cross-talk and negative cooperativity.
Main Methods:
- Integrated structural biology approach.
- Trapping of catalytic intermediates.
- Analysis of enzyme conformational changes at the atomic level.
Main Results:
- Identified a dynamic active-site "gating loop" in glutamate-1-semialdehyde aminomutase.
- Observed simultaneous open and closed states of the gating loop in different subunits during catalysis.
- Revealed a beta-sheet-to-alpha-helix transition in the gating loop.
- Characterized the communication triad involving the cofactor, interface helix, and gating loop.
Conclusions:
- The gating loop's conformational change facilitates substrate transport and active site formation.
- A molecular switch mechanism involving the cofactor, interface helix, and gating loop regulates enzyme activity.
- This mechanism explains the negative cooperativity observed in the enzyme's allosteric regulation.
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