title: Mutants of rat intestinal fatty acid-binding protein illustrate the critical role played by enthalpy-entropy compensation in ligand binding.
abstract: Site-specific variants of rat intestinal fatty acid-binding protein were constructed to identify the molecular interactions that are important for binding to fatty acids (FAs). Several variants displayed affinities that appeared incompatible with the crystal structure of the protein-FA complex. Thermodynamic measurements provided an explanation for these apparent inconsistencies and revealed that binding affinities often inaccurately reported changes in protein-FA interactions because changes in the binding entropy and enthalpy were usually compensatory. These results demonstrate that understanding the effects of amino acid replacements on ligand binding requires measurements of enthalpy and entropy, in addition to affinity.
authors.affiliation: Medical Biology Institute, La Jolla, California 92037, USA.
authors.forename: G V
authors.initials: GV
authors.lastname: Richieri
authors.forename: P J
authors.initials: PJ
authors.lastname: Low
authors.forename: R T
authors.initials: RT
authors.lastname: Ogata
authors.forename: A M
authors.initials: AM
authors.lastname: Kleinfeld
mesh_terms: D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D019277:Entropy; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D009154:Mutation; D018996:Myelin P2 Protein / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011485:Protein Binding / Q000235:genetics; D051381:Rats; D013816:Thermodynamics
chemical_list: D002352:Carrier Proteins; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D008024:Ligands; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins