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Molecular Determinants for Guanine Binding in GTP-Binding Proteins: A Data Mining and Quantum Chemical Study
1Department of Chemistry and Biochemistry, University of Toledo, Toledo, OH 43606, USA.
International Journal of Molecular Sciences
|November 27, 2024
Summary
GTP-binding proteins use diverse interactions like hydrogen bonds and cation-π forces to bind guanine, ensuring cellular signaling accuracy. Specific motifs aren't always required for this crucial guanine recognition.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- GTP-binding proteins act as molecular switches regulating cellular processes.
- Specific recognition of guanine is fundamental to their function.
Purpose of the Study:
- To identify the molecular determinants governing guanine recognition in GTP-binding proteins.
- To analyze the intermolecular interactions responsible for guanine binding.
Main Methods:
- Data mining of 298 GTP-binding protein complexes from the Protein Data Bank.
- Systematic analysis of intermolecular interactions.
- Quantification of interaction energies using the B2PLYP-D3/cc-pVDZ method.
Main Results:
- GTP-binding proteins utilize hydrogen bonding, cation-π, and π-π stacking interactions for guanine binding.
- Hydrogen bonds involving guanine's N2 and O6 atoms are key for specificity.
- Cation-π interactions with Lys/Arg and π-π stacking with aromatic residues enhance binding.
- The NKXD motif is not universally essential for guanine binding.
Conclusions:
- A combination of non-bonded interactions ensures specific and stable guanine recognition by GTP-binding proteins.
- Variability in interaction patterns allows effective guanine binding even without the NKXD motif.
- Understanding these interactions is crucial for comprehending cellular signaling and regulation.
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