Information theory analysis of the relationship between primary sequence structure and ligand recognition among a class of facilitated transporters.
Determining how specificity for a given ligand occurs among sequence and structurally related transporters is a fundamental problem in elucidating facilitated transport. It is likely that the specificity of a transporter for a ligand is defined by the primary amino acid sequence, and that different ligand specificities among highly related proteins are associated with variations in the amino acid sequence. To assist studies on the potential relationships between protein structure and ligand specificity, information theory was used to assign a measure that quantitates the importance of amino acid choice at individual sites in protein sequences based upon their variability. The approach allows for the transformation of a collection of multiply aligned sequences into a profile that provides a quantitative assessment of the relative frequencies of chemically similar residues at each site. Profiles generated from particular groups of proteins can be directly compared to profiles generated for other groups. These comparisons allow unique differences in the utilization of amino acids at individual sites to be identified as differences in information distribution. The approach was applied to the problem of identifying sites of the dopamine transporter which may play a role in distinguishing its ligand specificity and function from those of a related population of transporters for amino acid and amino-acid-like ligands. Several sites were identified that appear highly likely to distinguish the dopamine transporter from related proteins. Many of the sites identified were also found to be associated with predicted variations in local secondary and tertiary structure between the two classes of proteins.
Williamson
R M
RM
Department of Biotechnology, Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48106-1047, USA.
D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002352:Carrier Proteins / Q000502:physiology*; D004298:Dopamine / Q000737:chemistry; D007257:Information Theory; D011485:Protein Binding; D017433:Protein Structure, Secondary
D002352:Carrier Proteins; D004298:Dopamine