Biomaterial Database

Energetic origins of specificity of ligand binding in an interior nonpolar cavity of T4 lysozyme. 1995

A Morton, and W A Baase, and B W Matthews

Institute of Molecular Biology, Howard Hughes Medical Institute, Eugene, Oregon, USA.

To determine the constraints on interactions within the core of a folded protein, we have analyzed the binding of 91 different compounds to an internal cavity created in the interior of phage T4 lysozyme by site-directed mutagenesis [Eriksson et al. (1992a) Nature 355, 371-373]. The cavity is able to accommodate a variety of small, mainly nonpolar, ligands. Molecules which do not appear to bind include those that are very polar, those that are too large, and those that have appropriate volume and polarity but inappropriate shape. Calorimetric analysis of 16 of these ligands reveals that their free energies of binding are poorly correlated with their solvent-transfer free energies. In addition, their enthalpies of binding are much larger than expected on the basis of transfer of the ligands from an aqueous to a nonpolar liquid phase. The binding energetics were analyzed by dividing the reaction into three processes: desolvation, immobilization, and packing. This analysis indicates that all three processes contribute to binding specificity. For a subset of these ligands that are structurally related, however, packing interactions in the protein interior are well modeled by the interactions of the ligands with octanol.

UI	MeSH Term	Description	Entries
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D009113	Muramidase	A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 3.2.1.17.	Lysozyme,Leftose,N-Acetylmuramide Glycanhydrolase,Glycanhydrolase, N-Acetylmuramide,N Acetylmuramide Glycanhydrolase
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D002151	Calorimetry	The measurement of the quantity of heat involved in various processes, such as chemical reactions, changes of state, and formations of solutions, or in the determination of the heat capacities of substances. The fundamental unit of measurement is the joule or the calorie (4.184 joules). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
D013379	Substrate Specificity	A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.	Specificities, Substrate,Specificity, Substrate,Substrate Specificities
D013816	Thermodynamics	A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)	Thermodynamic
D017122	Bacteriophage T4	Virulent bacteriophage and type species of the genus T4-like phages, in the family MYOVIRIDAE. It infects E. coli and is the best known of the T-even phages. Its virion contains linear double-stranded DNA, terminally redundant and circularly permuted.	Bacteriophage T2,Coliphage T2,Coliphage T4,Enterobacteria phage T2,Enterobacteria phage T4,Phage T2,Phage T4,T2 Phage,T4 Phage,Phage, T2,Phage, T4,Phages, T2,Phages, T4,T2 Phages,T2, Enterobacteria phage,T4 Phages