Proteins 2 Flashcards
Which class of accesory proteins is responsible for catalysing disulfide interchne (shuffling of disulfide bonds until correct pairing is achieved)?
Protein disulfide isomerases
Which class of accesory proteins is responsible for catalysing the convertion of X-Pro peptide bonds between trans and cis conformations?
Peptidyl prolyl cis-trans isomerase
Which class of accesory proteins prevents improper folding and aggregation of proteins in internal hydrophobic regions?
Molecular chaperones
Heat shock proteins, chaperonins, calreticulin and lectins calnexin are examples of which kind of accesory protein?
Molecular chaperones
Why do most peptide bonds adopt the trans conformation?
There is less steric repulsion - a lower energy state
Why do X-Pro bonds adopt the cis conformation at higher rates?
Difference in steric repulsion between states is lower
What is the cause of Alzheimer’s?
Protein misfolding, a small protein aggregates in the brain and kills neurons
Prion diseases (like CJD, mad cow) cause what structural change in prion proteins?
Secondary alpha helical structures become beta sheets
Why is myoglobin found in high concentrations in skeletal and cardiac muscle cells?
A lot of oyxygen is required to generate the energy for muscle contraction
Myoglobin functions as
a store of oxygen that can be used readily
How was the 3D structure of myoglobin discovered?
Through the use of X-ray crystallography - 1957 John Kendrew
How many chains is hemoglobin made up of?
4
How many chains is hemoglobin made up of?
1
What is interesting about the fact that hemoglobin chains are similar to myoglobin?
Very different primary sequences can generate very similar structures
How many molecules of oxygen can hemoglobin bind?
4
one for each heme group on each polypeptide chain
Describe the structure of hemoglobin
4 polypeptide chains are packed tightlyin a tetrahedral array, forming a sphere held together by non covalent interaction
What structure is iron held within in the heme prosthetic group?
A protoporyphyrin IX ring structure
What are the 6 bonds that iron participates in in heme group?
4 nitrogen atoms of the poryphyrin ring
The proximal histidine residue
Oxygen
What are the functions of the distal histidine residue, (which is near the binding site of oxygen on the heme group)?
Reduces affinity for carbon monoxide
Prevents close contact of neighbouring heme groups - which would cause further oxidization of iron
Hemoglobin is an allosteric protein - what does this mean?
The binding of oxygen to one subunit causes a conformational change in the other subunits
Why is the binding of oxygen to hemoglobin ‘cooperative’?
Binding to one subunit raises the affinity of the other units for oxygen
Which protein has a higher affinity for oxygen, myoglobin or hemoglobin?
Myglobin
What is the shape of the oxygen dissociation curve for myoglobin?
hyperbolic
What is the shape of the oxygen dissociation curve for hemoglobin?
sigmoidal
Why is oxygen released from hemoglobin and absorbed by myoglobin in blood capillaries?
Because myoglobin has a higher affinity for oxygen
What is oxyhemoglobin?
Hemoglobin with 4 molecules of oxygen bound
Binding of oxygen to deoxyhemoglobin causes __ to break and reform
The ionic interactions that hold together the subunits
What is the Bohr effect?
The fact that the concentration of protons and caerbon dioxide in surrounding tissue affects the binding of oxygen
Concentrations of protons and carbon dioxide are high in metabolically active tissues such as muscle. What happens to the dissociation curve of hemoglobin?
It shifts to the right. The release of oxygen is promoted
The conformation of deoxyhemoglobin is preferred over that of oxyhemoglobin when in the presence of high concentrations of which 3 species?
Protons, carbon dioxide and BPG(bisphosphoglycerate)
Preference of deoxyhemoglobin conformartion causes the _
Release of oxygen
Why do high concentrations of carbon dioxide increase concentrations of protons?
Because of the action of carbonic anhydrase
What does carbonic anhydrase catalyse?
The conversion between carbon dioxide + water and carbonic acid + protons + bicarbonate ions
Proton binding sites on hemoglobin have _
A higher affinity for protons in the deoxyhemoglobin conformation
What is the effect of the presence of BPG in erythrocytes?
It reduces the affinity of hemoglobin for oxygen, thereby promoting its release
How does BPG bind with hemoglobin?
It enters the central cvity, forming ionic bonds with positively charged amino acid side chains
Molecules that favor deoxyhemoglobin over oxyhemoglobin are examples of _
Allosteric effectors
Which highly anionic organic phosphate molecule is present in erythrocytes?
2,3-bisphosphoglycerate
Why are the effects of BPG, carbon dioxide and protons additive?
They act at different sites, so are not in competition
What is the difference in tructure between HbA and HbF
HbA - 2 alpha chains, 2 beta chains
HbF - 2 alpha chains, 2 gamma chains
Why does HbF have a higher affinity for oxygen the HbA?
Because it binds less BPG
Higher affinity of HbF for oxygen optimises _
The transfer of oxygen from maternal circulation to fetl circulation across placenta
What change in hemoglobin synthesis occurs near birth?
Synthesis of gamma chains is switched off
Synthesis of beta chains is switched on
Describe HbS (sickle cell) molecules. What is the effect on cells?
They are long and fibrous, distorting the shape of erythrocytes
What is conservative substitution?
The replacement of an amino acid residue by another with similar properties
What is the fundamental alteration of hemoglobin molecules that characterises sickle cell anemia?
Non conservative substitution is made of a polar residue with a hydrophobic one
Why do homozygotes of sickle cell anemia have lower lifespans?
There is a high risk of infection, cardiac failure etc
Due to the distorted shape of erythrocytes causing blockages in small blood vessels
What percentage of erythrocytes are sickle cells for homozygotes and heterozygotes?
50% for homozygotes
1% for heterozygotes
Why are rates of sickle cell anemia high in Africa?
Heterozygotes give protection against the most lethal forms of malaria
