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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
On the conservation of protein sequences in evolution.
B Kisters-Woike1, C Vangierdegom, B Müller-Hill
1Institut für Genetik der Universität zu Köln, Weyertal 121, D-50931 Köln, Germany. b.kisters@uni-koeln.de
Trends in Biochemical Sciences
|September 6, 2000
Summary
Enzyme amino acid sequences, such as alcohol dehydrogenase, are highly conserved due to their function within multi-enzyme complexes. These protein interactions limit evolutionary changes on enzyme surfaces, preserving their structure and function across species.
Area of Science:
- Biochemistry
- Evolutionary Biology
- Molecular Biology
Background:
- Enzymes like alcohol dehydrogenase (ADH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) exhibit remarkable amino acid sequence conservation across diverse phyla.
- This high degree of conservation suggests underlying functional or structural constraints that limit evolutionary divergence.
Purpose of the Study:
- To propose a hypothesis explaining the strong amino acid conservation observed in key metabolic enzymes.
- To investigate the potential role of multi-enzyme complex formation in constraining protein evolution.
Main Methods:
- Comparative sequence analysis of conserved enzymes across different species.
- Bioinformatic analysis to identify conserved surface residues and interaction interfaces.
- Literature review on the quaternary structure and functional interactions of ADH and GAPDH.
Main Results:
- Strong conservation of amino acid sequences for ADH and GAPDH confirmed across a wide range of organisms.
- Evidence suggests these enzymes frequently participate in multi-enzyme complexes.
- Surface residues critical for protein-protein interactions show particularly high conservation.
Conclusions:
- The formation of multi-enzyme complexes is a significant factor driving the evolutionary conservation of enzyme amino acid sequences.
- Interactions within these complexes impose structural constraints, limiting the permissible mutations on enzyme surfaces.
- This mechanism provides a robust explanation for the observed evolutionary stasis of essential metabolic enzymes.
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