A ligand-centric analysis of the diversity and evolution of protein-ligand relationships in E.coli.
As enzymes evolve and diverge from common ancestor sequences, they often keep their overall reaction chemistry but specialize in the binding of different cognate ligands. This study borrows methods for the computational assessment of 2D similarity of small molecules from the field of chemoinformatics, to examine the extent of structure conservation of cognate ligands binding to similar proteins. Proteins from 87 structural superfamilies from Escherichia coli form the core dataset, which is extended using homologues with functional assignments from any organism. We find that correlation of the substrate similarity with protein similarity (measured by either sequence-based or structure-based scores) can only be clearly established for very similar proteins. At low sequence identities, the superfamily to which a protein belongs can give helpful clues to its function, and more importantly, the confidence attached to such clues is superfamily-dependent. Our data indicate that only a few superfamilies show great substrate diversity, and that most exhibit conservation of at least part of the structural scaffold of the substrate.
Nobeli
Irene
I
EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. nobeli@ebi.ac.uk
Spriggs
Ruth V
RV
George
Richard A
RA
Thornton
Janet M
JM
D030562:Databases, Protein; D004926:Escherichia coli / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D013379:Substrate Specificity
D029968:Escherichia coli Proteins; D008024:Ligands