Amino acids, peptides, and protein III LO Flashcards
what forms a tertiary structure?
interactions between secondary structures
what are the 2 major classes of tertiary structures?
fibrous and globular proteins
what is a quaternary structure?
multiple polypeptide chains that come together to form a functional protein
what are the common amino acids in loops and turns?
glycine and proline
what is the difference between a loop and a turn?
turn is shorter and loop is longer sequence of AA
why are glycine and proline the amino acids that are present in turns and loops?
- glycine has small R group with no side chains to react with other AA
- proline cannot hydrogen bond due to covalent bond between nitrogen and alpha carbon
what are the characteristics of a beta turn?
- 180 degree turn over 4 amino acids
- stabilized by H bond from carbonyl O of 1st AA and amide of 4th AA
- proline in position 2 or glycine in position 3 are common
why are loops and turns important in a proteins function?
because it determines the 3D structure of the protein which ultimately determines its function
what is Kd?
dissociation constant
what does the Kd represent in a protein-ligand binding scenario?
concentration at which 50% of ligand is bound to protein
what is the relationship between Kd and the affinity of the protein for the ligand?
small Kd = more tightly bound ligand due to high affinity for protein
as Kd increases, what must happen to the amount of ligand in the solution to achieve 50% binding?
more ligand must be present
what is the equation for calculating Kd?
Kd = [protein][ligand] / [ligand-protein complex]
what are the characteristics of fibrous proteins?
insoluble, made from a single secondary structure (a helix or b sheet)
what are the characteristics of globular proteins?
water soluble globular proteins and lipid soluble membranous proteins
what type of tertiary proteins are most common within the body?
globular proteins
what is the function of loops in the V regions of antibodies and what is the significance of this?
binds antigens
shows that loops can have functions that aren’t just associated with protein folding
what are the 4 characteristics similar between protein and ligand that achieve high specificity?
- size
- shape
- charge
- hydrophobic/hydrophillic character
what are the 2 models for binding specificity?
- lock and key model
2. induce fit model
who developed the lock and key model?
emil fisher
who developed the induced fit model?
daniel koshland
what is the lock and key model?
there is complementarity that is preformed between ligand and protein and this is why they fit together
what is the induced fit model?
- proteins affinity for the ligand increases once the ligand binds due to conformational change
- ligand and protein can both change their conformations to induce this high specificity
- can increase the affinity of the protein for a second ligand
how is heme situated with myoglobin in order to bind oxygen?
- located deep within the protein in the cyclic porphyrin ring
- contains divalent iron molecule coordinated with histidine and oxygen
- this configuration ensures that iron doesn’t become oxidized thus losing it’s affinity for oxygen
what binds better to heme than oxygen?
carbon monoxide
why is carbon monoxide poisoning bad?
carbon monoxide binds tighter than oxygen and once bound does not dissociate from heme. oxygen can therefore not be transported in the body because CO is bound instead
what cellular aspect of mitochondria does CO also affect?
cytochromes in the electron transport chain
what subunits is hemoglobin made up of?
2 alpha and 2 beta subunits
what is positive cooperativity?
when one oxygen molecule binds to hemoglobin, the other 3 sites increase their affinity for oxygen (opposite for negative cooperativity)
how can positive cooperativity be recognized on paper?
sigmoidal binding curves
what state is hemoglobin in when it has no oxygen bound?
T state (tense state)
what state is hemoglobin in after the 1st oxygen molecule binds?
R state (relaxed state)
what drives oxygen to leave hemoglobin?
concentration and partial pressure gradients
what is a one word answer to explain why hemoglobin makes a good transporter of oxygen?
cooperativity
how does pH affect the binding of oxygen to hemoglobin?
- high pH increases affinity
- lower pH decreases affinity
what increases the oxygen transfer efficiency?
Bohr Effect
what is the Bohr Effect?
there is a pH difference between the lungs and tissues
how is carbon dioxide carried back to the lungs?
as bicarbonate in blood or attached as carbamate on amino terminal residues of each hemoglobin subunit
what is the most important part of x-ray cyrstallography in identifying proteins?
crystallizing the protein
what are 2 reasons that we as clinicians need to know what the structures of protein are?
- understand how proteins work
2. structure-based or structure-guided drug design
