1.2 Protein structure, ligand binding and conformational change Flashcards
Amino acids
Amino acid sequence determines protein structure. Proteins are polymers of amino acid monomers.
Amino acids are linked by peptide bonds to form polypeptides.
Amino acids have the same basic structure, differing only in the R group present.
R groups
R groups of amino acids vary in size, shape, charge, hydrogen bonding capacity and chemical reactivity.
Amino acids are classified according to their R groups: basic (positively charged); acidic (negatively charged); polar; hydrophobic
The wide range of functions carried out by proteins results from the diversity of R groups.
Primary structure
The sequence in which the amino acids are synthesised into the polypeptide
Hydrogen bonding
Along the backbone of the protein strand results in the regions of secondary structure - alpha helices, parallel or anti-parallel beta-pleated sheets, or turns.
What does a polypeptide fold into?
The polypeptide folds into a tertiary structure.
This conformation is stabilised by interactions between R groups: hydrophobic interactions; ionic bonds; London Dispersion forces; hydrogen bonds; disulphide bridges (covalent bonds between between R groups containing sulphur).
Quaternary structure
This structure exists in proteins with two or more connected polypeptide subunits.
It describes the spatial arrangement of the subunits.
Prosthetic group
Is a non protein unit tightly bound to a protein and necessary for its function. For example, the ability of haemoglobin to bind oxygen is dependant upon the non-protein haem group.
R groups interactions can be influenced by pH and temperature.
Increasing temperature disrupts the interactions that hold the protein in shape; the protein begins to unfold, eventually becoming denatured. The charges on acidic and basic R groups are affected by pH. As pH increases or decreases from optimum , the normal ionic interactions between charged groups are lost, which gradually changes the conformation of the protein until it becomes denatured.
Ligands
A ligand is a substance that can bind to a protein.
R groups not involved in protein folding can allow binding to ligands.
Binding sites will have complementary shape and chemistry to the ligand.
As a ligand binds to a protein-binding site the conformation of the protein changes.
This change in conformation causes a functional change in the protein.
Allosteric interactions
Allosteric interactions occur between spatially distinct site.
The binding of a substrate molecule to one active site of an allosteric enzyme increases the affinity of the other active sites for binding of subsequent substrate molecules. This is of biological importance because the activity of allosteric enzymes can vary greatly with small changes in substrate concentration.
Allosteric proteins
Many allosteric proteins consist of multiple subunits (have a quaternary structure).
Allosteric proteins with multiple subunits show co-operativity in binding, in which changes in binding at one sub unit alter the affinity of the remaining subunits.
Allosteric enzymes contain a second type of site, called an allosteric site.
Modulators
Following binding of a modulator, the conformation of the enzyme changes and this alters the affinity of the active site for the substrate.
Positive modulators increase then enzymes affinity for the substrate, whereas negative modulators reduce the enzymes affinity.
Co-operativity
The binding and release of oxygen in haemoglobin shows co-operativity. Changes in binding of oxygen at one subunit alter the affinity of the remaining subunits for oxygen.
influence and physiological importance of Temperature and pH effect on binding of oxygen
A decrease in pH or an increase in temperature lowers the affinity of haemoglobin for oxygen, so the binding of oxygen is reduced. Reduced pH and increased temperature in actively respiring tissue will reduce the binding of oxygen to haemoglobin promoting increased oxygen delivery to tissue.
Addition or removal of an phosphate
The addition or removal of phosphate can cause reversible conformational change in proteins. This is a common form of post-transitional modification.
The protein kinase catalyse the transfer of a phosphate group to other proteins.
The terminal phosphate of ATP is transferred to specific R groups.
Protein phosphatases catalyses the reverse reaction.
