Flashcards in Chapter 2 Notes Deck (56):
Amino acids are composed of what 4 groups?
What determines which carboxy group dissociates first on an amino acid?
Positive charges on the amino groups in close proximity cause repulsion. This determines which COOH proton will dissociate first.
Which amino acids are mostly used as buffers?
Glycine and histidine
How do you determine the isoelectric point?
Simplest amino acid?
Difference between alanine and glycine?
Alanine is and glycine is achiral
What are the nonpolar amino acids?
Valine, leucine, isoluecine, methionine, phenylalanine, tyrosine, tryptophan
Which amino acid is involved in stronger VDW interactions in its interior due to its long side chains?
What makes proline so different from the other amino acids?
It has a conformationally restricted ring structure that causes kinks in polypeptide chain because its side chain is bonded to both the amino group and alpha carbon.
Which amino acids can be absorbed by light and read in a Spec?
Phenylalanine, tyrosine, tryptophan
What is the hydrophobicity ranking of the light absorbing amino acids? Why?
Phe > Tyr > Trp
Phe has side chain that is more hydrophobic. Trp has an indole group that is highly reactive and can deprotonate. Tyr has a hydroxyl group that makes it more polar and highly reactive.
What are the polar, uncharged amino acids?
Serine, threonine, asparagine, glutamine
What interactions are taking place in Phe, Tyr, and Trp?
What interactions are taking place in Serine and threonine?
What is interesting about cysteine?
Similar to Serine structurally but has a highly reactive sulfhydryl group (can form disulfide bonds in proteins -- important for stabilizing protein structures); disulfide bonds are formed by cross linking by oxidation of a pair of cysteines
T/F: Extracellular proteins don't have disulfide bonds, whereas intracellular proteins do not.
What are the polar charged amino acids?
Lysine, arginine, histidine, aspartate, glutamate
What is special about histidine?
It has an imidazole group that has a pka of 6 and is found in the active sites of enzymes. Proteins will change the pH of histidine from neutral pH to 8 so it can be involved in enzymatic functions (reactions)
Known as the basic AA?
How does pka play a role in HIV protease drug design?
Can stop HIV spread by dimer of aspartic acid groups in close proximity (active sites) that reduces the effects of the enzyme.
One is protonated and one is not (aspartic acid) because of a mechanism used to cleave peptides (modifies the surrounding protein environment)
What are the negatively charged vs positively charged polar amino acids?
Negative: aspartate, glutamate
Positive: Lysine, arginine, histidine
How are two amino acids linked?
Via peptide bonds accompanied by loss of water. The linkage is between an alpha carboxy group of one AA with an alpha amino group of another AA. It is not hydrolysis back in water into an individual AA, making it more stable.
Describe the N and C terminal ends of a polypeptide chain.
N-terminus: positively charged polar
C-terminus: negatively charged polar
The reduced form of ___ prevents cystine from making cysteine disulfide bonds. Why?
Glutathione; because reduction of disulfide bonds between cysteines is common in intracellular proteins NOT extracellular proteins
Give an example of a highly disulfide cross-linked polypeptide?
Insulin because of its intrachain disulfide bonds
What is the geometry of a peptide bond?
Planar because of considerable double-bond character.
Describe the rotations in peptide bonds.
Free rotation about the C=N bond is not possible, which constrains the conformation of the peptide backbone. Free rotation about the other 2 bonds in the peptide is allowed because they are single bonds.
The angle of rotation about the bond between the nitrogen and alpha carbon atoms.
The angle of rotation about the bond between the alpha carbon and the carbonyl carbon atoms
Omega dihedral (torsion) angles?
A measure of the rotation about a bond, usually taken to lie between -180 and +180 degrees
Most AA prefer ___ orientation because of steric clash of R-groups. The exception to this is ___.
Proline-can be in both orientations because steric clashes are the same
Which two AA do not follow the Ramachandran plot pattern and why?
Proline and glycine because they have too short side chains
How is the alpha helix stabilized?
By hydrogen bonding between the NH and CO groups of the main chain. The C=O group from residue n is hydrogen bonded to the NH group from residue n+4
Which AA are preferred for the alpha helix?
Ala, Leu, Met, Glu, Gln, His, Lys, Arg
Why are the other AA less preferred?
Tyr, Trp, Phe, Ile, Val, Thr: large bulky side chains
Gly: side chain is H is too small to protect the backbone
Pro: side chained linked to alpha-N, has no NH to H-bond and has a rigid ring structure
Asp, Asn, Ser: H-bonding side chains compete directly
Are right or left-handed helices more common?
Right-handed because side chains project outwards and still remain close to NH of backbone
Side chains closer to CO than NH groups in left-handed causing more steric diversion and repulsion making it less stable.
What is the difference between antiparallel and parallel beta sheets?
Antiparallel: stabilized by interchain hydrogen bonds between two polypeptide strands
Parallel: hydrogen bonding pattern different (crooked, at an angle because hydrogen bond is formed from the amino group of 1 AA and the carbonyl group from a different AA strand.
Difference between a beta loop and a beta turn?
Loop: more lucid in nature
Turn: connects one beta strand with another beta strand; changes direction tighly; consists of small residues (Pro, Gly, Asn, Ser, Asp)
How is a salt bridge formed?
When two cysteines are in close proximity, they have a sulfide crosslinkage, hydrogen bonding, and a hydrophobic interaction
Myoglobin has __ AA on the inside and ___ AA on the outside.
What makes porin different from myoglobin?
It has a distribution of hydrophobic and hydrophilic AA which are opposite from myoglobin, because not surrounded by water but instead surrounded by a membrane which has a water filled hydrophilic channel to allow molecules to diffuse from one side to another
Difference between tertiary and quaternary structure?
Teritiary: proteins made up of multiple domains within one polypeptide chain
Quaternary: proteins made up of multiple domains on many polypeptide chains
__ binds oxygen.
What is the reason for the symmetric structure of the common cold virus: rhinovirus?
limited DNA and use of genes as efficiently as possible
How are host cells infected by Dengue Virus?
structure of dengue virus is similar to other viruses, but E+M proteins come together to form a tetradimer where a pocket forms in the center and used a histidine mechanism where 2 are in the center and used to modulate when it is infectious and when it isn't (based on pH)
What did Anifinsen use to study protein folding?
What information is necessary for the protein to fold?
the AA sequence of a protein determines its tertiary structure
What occurred when Anfinsen added beta-mercaptoethanol to the ribonuclease?
it didn't completely unfold the protein - only weakened it by breaking the disulfide bonds in the protein (reduction)
What occurred when Anfinsen added urea to the already reduced ribonuclease by the addition of beta-mercaptoethanol?
denatured the protein, allowing for the structures of random coils to be observed
What occurred when refolding of ribonuclease by reoxidation and dialysis of urea?
full enzymatic activity restored
What occurred when refolding by reoxidation but in the presence of urea only?
resulted in a protein with only 1% activity due to the many possible combinations of disulfide bonds and incorrect sterics of disulfide bonds
With the further addition of beta-mercaptoethanol in the presence of urea with ribonuclease, what occurred?
resulted in correctly folded protein
What can misfolding of proteins cause?
alpha-helical misfolding forms of beta strands and draws more to produce a beta-sheet (of prion proteins) to form amyloid plaques
What is the proposed pathway of chymotrypsin inhibitor? More broadly speaking: nucleation condensation folding
protein folding is a highly cooperative process; may involve formation of several stable intermediates before reaching the native conformation from the denatured form; occurs in miliseconds (slows down by lowering the temperature, trapping intermediates, etc.