Protein Function: Ligand Binding and Allosteric Regulation

Ligand

A molecule or ion bound by another molecule

Cooperative ligand binding

Binding of a ligand to one site affects the properties of other binding sites

Binding

Specific interactions between molecular surfaces

Shape complementarity

Van der Waals interactions

Chemical complementarity

Hydrogen bonds, salt linkages

Hydrophobic effect

Hydrophobic ligand binding in a hydrophobic site in protein

Equilibrium dissociation constant Kd

Concentration of ligand needed to half-saturate binding sites

Fractional saturation

Fraction of total binding sites occupied by ligand

Rectangular hyperbola

Plot of fractional saturation vs. ligand concentration

Partial pressure of oxygen gas (pO2)

Proportional to oxygen concentration in the atmosphere

Myoglobin (Mb)

Binds and stores oxygen in muscle tissue

Hemoglobin (Hb)

Transports oxygen from lungs to tissues

Globin fold

Tertiary structure of myoglobin and hemoglobin

Heterotetramer

Hb structure with 2 alpha and 2 beta subunits

Quaternary structure

Arrangement of subunits in Hb

Prosthetic group

Compound tightly bound to a protein required for its function

Cooperative binding

Communication between ligand binding sites on a protein

Bohr effect

Proton and CO2 binding reduce O2 affinity of Hb

2,3-bisphosphoglycerate (2,3-BPG)

Metabolite that reduces O2 affinity of Hb

Fetal hemoglobin

Binds O2 more tightly than adult hemoglobin

HbS (sickle hemoglobin)

Mutant hemoglobin causing sickle cell anemia

Methemoglobin

Hb with oxidized iron (Fe3+), unable to transport O2

Mutant hemoglobins

Hemoglobins with single amino acid substitutions