Chapter 5 Function of Globular Protein Flashcards
Explain under protein flexibility the concept of different types of movements
Fastest: Atomic fluctuations such as interatomic vibrations.
Intermediate: Collective motions of bonded and non-bonded neighboring groups of atoms, such as wig-wag motions of long side chains or the flip-flopping of short peptide loops.
Slowest: Large scale ligand-induced conformational changes of whole domains.
The function of my proteins involve reversibly binding to other molecules called _______. Explain some of their properties and how they effect proteins.
Ligands
Can be any other molecule/protein
Causes a conformational change
When binding of a ligand causes a protein to change from an inactive to an active conformation, the process is called ___________.
Induced fit
To avoid oxidation, iron is often incorporated into a protein-bound prosthetic group called _____, which consists of a complex organic ring structure called __________ and is bound a single in ferrous state
Heme
Protoporphyrin
Iron atom (Fe2+)
Explain how iron is a component in heme.
Nitrogen on the porphyrin ring have a proton donating effect along with the Nitrogen side chain in Histidine, prevents the oxidation of the heme iron (F3+).
In protein-ligand interaction, explain theta
theta is the fraction of the ligand-binding sites on the protein occupied by the ligand.
binding site occupied divided by the total binding site.
the hyperbolic function of [L]
In protein-ligand interaction, explain Kd
Kd is equal to 1/Ka, or [L] at which half the binding sites are occupied (theta = 0.5)
Kd is the ligand concentration at which half the binding sites on protein are occupied by ligand. Higher the Kd, lower the affinity of ligand for protein.
Explain some of the aspects to protein structure affecting ligand binding in O2, CO2 and the iron in heme.
Binding of a ligand to protein is dependent on the structure of protein and is often accompanied by conformational changes.
Heme can bind to both CO2 and O2.
Kd of free form heme has a much higher affinity for O2 than CO2, but when bound to myoglobin that is dramatically reduced.
When O2 binds to the iron it is at an angle allowing H-bond with Histidine E7, but when CO2 binds, it occurs in a straight line, not allowing H-bond.
For breathing, O2 exhibit constant conformational change with heme molecule.
Explain some of the aspects to protein structure affecting ligand binding in O2, CO2 and the iron in heme.
Binding of a ligand to protein is dependent on the structure of protein and is often accompanied by conformational changes.
Heme can bind to both CO2 and O2.
Kd of free form heme has a much higher affinity for O2 than CO2, but when bound to myoglobin that is dramatically reduced.
When O2 binds to the iron it is at an angle allowing H-bond with Histidine E7, but when CO2 binds, it occurs in a straight line, not allowing H-bond.
For breathing, O2 exhibit constant conformational change with heme molecule.
Hemoglobin are ____________ cells, meaning they reduced their function to a particular task.
vestigial
Explain the differences between myoglobin and hemoglobin with their affinity for O2 in terms of graphs.
Myoglobin, with a hyperbolic O2-binding curve, is less sensitive to changes in the concentration of dissolved O2 which suits its role as O2- storage protein.
In contrast, hemoglobin with a sigmoid O2-binding curve, is very sensitive to changes in dissolved O2 and is therefore more suited to carry O2 in blood.
What are the 2 major conformations of hemoglobin? explain how they function.
(1) Relaxed state (R-state) which binds O2 with a higher affinity. Binding of O2 stabilizes R-state.
(2) Tense state (T-state) which is the stable form when O2 is absent, and is the predominant conformation of deoxyhemoglobin.
Explain the conformational change between R and T state that gives it the binding capacity for O2.
Transition from T to R is triggered by changes in the positions of key amino acid side chains surrounding the heme. In T-state heme porphyrin is slightly puckered, causing heme iron to protrude somewhat towards His F8. Binding of O2 causes heme to become more planar and position of His F8 and attached F helix changes.
Why is hemoglobin the O2 carrying protein in blood?
To carry O2 from lung to sink tissues, a protein is needed that is able to bind O2 efficiently in lung and release it efficiently in the body tissues. An O2 carrying protein with such qualities is expected to have a ‘Sigmoid’ O2 binding curve
The ability of hemoglobin to switch its binding efficiency for O2 between low and high affinity states is due to its ____________ nature.
allosteric
