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Updated: Jul 19, 2026
09:30
Modeling Ligands into Maps Derived from Electron Cryomicroscopy
Published on: July 19, 2024
Cognate ligand domain mapping for enzymes.
Matthew Bashton1, Irene Nobeli, Janet M Thornton
1EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. bashton@ebi.ac.uk
Journal of Molecular Biology
|October 13, 2006
Summary
This study introduces an automated method to identify enzyme-ligand relationships using structural data. It reveals common binding patterns and highlights the importance of co-factors in enzyme function.
Area of Science:
- Biochemistry
- Structural Biology
- Bioinformatics
Background:
- Enzyme function is intrinsically linked to ligand binding.
- Understanding enzyme-ligand interactions is crucial for drug discovery and understanding biological processes.
- Current methods for identifying cognate ligands are often manual and time-consuming.
Purpose of the Study:
- To develop an automated procedure for assigning potential cognate ligands to protein domains.
- To create a database (PROCOGNATE) mapping ligands to enzyme structures and superfamilies.
- To analyze ligand-binding modes and their implications for protein evolution and function.
Main Methods:
- Utilized structural data from the Protein Data Bank (PDB).
- Developed a two-step procedure: assigning PDB ligands to domains, then comparing chemical similarity to KEGG ligands.
- Incorporated Enzyme Commission (EC) numbers for accurate cognate ligand assignment.
Main Results:
- The PROCOGNATE database contains mappings for 3277 (4118) protein structures and 351 (302) superfamilies (CATH/SCOP).
- Approximately half of ligands bind to a single domain, while 16% bind to multiple domains.
- Common crystallization buffer components are prevalent non-cognate ligands in PDB, whereas essential co-factors like NADH, FADH2, and ATP are frequent cognate ligands.
Conclusions:
- Automated cognate ligand assignment is feasible and aids in understanding enzyme-ligand relationships.
- Ligand-binding modes influence domain recombination and protein function evolution.
- The prevalence of adenine ribonucleotide-containing co-factors suggests convergent evolution in ligand-binding domains.
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