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X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
Published on: May 13, 2020
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The modular structure of ThDP-dependent enzymes.
Constantin Vogel1, Jürgen Pleiss
1Institute of Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Proteins
|June 4, 2014
Summary
Thiamine diphosphate (ThDP)-dependent enzymes exhibit diverse structures and functions, classified into nine superfamilies. This study reveals conserved residues and proposes an evolutionary pathway explaining their diversity.
Area of Science:
- Biochemistry
- Structural Biology
- Evolutionary Biology
Background:
- Thiamine diphosphate (ThDP)-dependent enzymes are a diverse protein family crucial in various metabolic pathways.
- These enzymes are characterized by the ThDP cofactor binding at the interface of PYR and PP catalytic domains.
- Existing classification includes nine superfamilies with varying structural architectures.
Purpose of the Study:
- To classify ThDP-dependent enzymes based on their structural architectures.
- To identify conserved residues within the PYR and PP domains.
- To propose an evolutionary pathway for the diversification of ThDP-dependent enzymes.
Main Methods:
- Structure-based domain alignment of over 62,000 PYR and PP domain sequences.
- Analysis of cofactor binding sites and conserved residues.
- Comparative analysis of domain arrangements across different superfamilies.
Main Results:
- Nine superfamilies of ThDP-dependent enzymes were assigned to five distinct structural architectures.
- Two superfamilies feature separate PYR and PP domains, while others show intra- or inter-monomer domain arrangements.
- Seven highly conserved positions were identified, including the GDGX(24,27)N motif and key residues for cofactor binding and activation.
- An evolutionary pathway involving domain recruitment, linkage, and rearrangement was proposed.
Conclusions:
- The structural diversity of ThDP-dependent enzymes arises from variations in domain arrangement and evolutionary events.
- Conserved residues highlight critical functional sites within the catalytic domains.
- The proposed evolutionary model provides a framework for understanding the expansion and diversification of this enzyme family.
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