Protein Structure and Function Flashcards
What is the diagnostic test for CF? What is a normal value?
Sweat test Normal = < 40
How do uncharged polar amino acids behave?
Zero net charge at physiologic pH (7.4) R groups form hydrogen bonds with water
How do proteins fold?
Naturally, to reach lowest energy state With the help of chaperone proteins
When is an amino acid a zwitterion?
At pH 7 charge is balanced between + and - forms
Which amino acids tend to cluster stabilizing proteins through hydrophobic interactions?
Alanine Valine Leucine Isoleucine (last 3 are branched chain AAs)
How is pI calculated for nonionizable R groups?
= (pka1 + pka2) / 2
What is a “motif”? Does it have function?
Classified as (recognizable) folding patterns which may include multiple secondary structures e.g. helix-turn-helix Motifs do not have inherent function
Which AAs can act as attachment sites for oligosaccharides and glycoproteins? What group do they attach to?
Asn - amide group
Ser - hydroxyl group
Thr - hydroxyl group
What is an example of a “disordered” protein? What does this mean?
p53 tumor suppressor Is disorganized and flexible, usually means it can bind to multiple things
What are stabilizing influences to protein structure?
Most important: sequence! Chemical properties Covalent and disulfide bonds Hydrophobic interactions Van der Waals forces Electrostatic forces
What indicates a strong acid?
Small pKa
Do proteins play a major role in the buffering system of cells and plasma?
yes
Which AAs have ionizable side chains?
Lysine
Arginine
Tyrosine
Cysteine
Histidine
What AAs promote the alpha helix? Which ones do not?
Promote: Met, Ala, Leu Destabilize: Asp, His, Lys (charged) Pro Glu
Describe the beta sheet:
Composed of 2 or more regions of one OR MORE polypeptide chains R groups can be above or below plane of sheet
What is the isoelectric point (pI)?
The point at which proteins and some amino acids are electrically neutral
What is the quaternary structure of proteins?
Arrangement of 2 or more polypeptide chains/subunits
What are three new CF drugs?
Ivacaftor Dornase alfa Orkambi (helps deltaF508 patients!)
What is the bond between amino acids?
Peptide bond
What is the basic structure of an amino acid?
Carbon with 1 H, a Carboxyl group, an amino group + VARIABLE R group
What is the secondary structure of amino acids?
Alpha helix Beta sheet Loops Coils
Which AAs cause MSUD when they fail to be broken down? What do they have in common with one another?
Branched chain AAs! Valine Leucine Isoleucine
What are two general categories of proteins?
Fibrous, Globular
What do globular proteins do?
Enzymes, regulatory proteins, immunoglobulins, transport proteins, motor proteins, etc.
Which amino acid forms disulfide (S-S) bonds? Are these especially strong bonds?
Cysteine YES! Can be formed between 1 or 2 polypeptides
What elevated protein is indicative (but not diagnostic) of cystic fibrosis? Where is it produced?
Immunoreactive Trypsinogen (IRT) Produced by the pancreas
Which AA is barely charged and what is it good for?
Histidine is weakly basic and thus makes a good buffer
Which AAs have polar hydroxyl groups that can be attachment sites for groups (e.g. phosphate)?
Serine Threonine Tyrosine
What is a protein domain? Does it have function?
Regions of polypeptide chains that can fold stably and independently with respect to the protein. Has function even outside of the protein as a whole!
Describe the structure of globular proteins
Polypeptide strands folded into globular shape, tend to have complex tertiary structures e.g. myoglobin and hemoglobin
How is Ka calculated? pKa?
Ka = [H][A]/ [HA] pKa = - log Ka
What is the unique feature of proline?
It is large and bulky and thus not flexible
How are peptide bonds form?
Carboxyl group attacks amino group, water is formed
What is Maple Syrup Urine Disease (MSUD)?
Build up of alpha-keto acids due to failure of branched chain alpha-keto acid DH complex (enzyme that breaks down branched chain amino acids)
Can beta sheets be parallel or antiparallel?
Yes!
What are the 4 groupings of amino acids?
Non polar Polar uncharged Positively charged Negatively charged
Describe structure of fibrous proteins
Tend to contain one form of secondary structure and little tertiary structure Tend to be hydrophobic (e.g. collagen)
What is unique about glycine?
It is very small (R group is just a hydrogen) and thus tiny and can make tight turns/is flexible
What are uncharged polar amino acids?
Asparagine Glutamine Cysteine Serine Threonine Tyrosine
How many classes of CF are there? What is the most common (85%)?
6 Class II - (delta)F508 phenylalanine deletion
What determines the primary structure of amino acids?
Sequence (which includes all covalent bonds: peptide and disulfide)
What are characteristics of nonpolar amino acids?
- Hydrophobic 2. Do not participate in hydrogen bonding or ionic bonding? 3. Do not accept or donate protons
How is pI calculated for ionizable R groups?
= (pKaNH31 + pKaNH32) / 2 OR = (pKaCOO1 + pKaCOO2) / 2
What does pKa mean functionally?
The pH at which points the molecule is 50% in the acid form and 50% in the base form
What are the positively charged polar AAs?
Lysine Arginine Histidine (BARELY basic)
What causes CF?
Single mutation in Cystic Fibrosis Transmembrane conductance Regulator (CTFR) gene Causes malfunction in chloride transport and an increase sodium (and thus water) absorption across epithelial cells. This leaves behind a viscous/dry medium in the airway This is also a very favorable environment for bacterial growth
What does pKa indicate?
The relative strength of a weak acid or base
What is a common AA in enzyme active sites?
Cysteine
Is the carboxyl group a stronger acid than the amino group?
Yes
What are the branched chain amino acids?
Valine Leucine Isoleucine
What do fibrous proteins do?
Provide structural support, external protection, shape, flexibility, etc.
Describe the alpha helix:
Secondary structure 3.6 AA residues per turn R groups stick out from helix
What are the nonpolar amino acids?
Glycine Alanine Valine Leucine Isoleucine Proline Phenylalanine Tryptophan Methionine GAV LIPPTM
What are the negatively charged polar AAs?
Aspartic acid Glutamic Acid
What is the tertiary structure of proteins?
Folding to give 3D form Net effect of many weak interactions and disulfide bonds Hydrophobic residues get buried
What occurs at point A?
Both amino and carboxyl group are protonated
What happens at point B?
pKa of the carboxyl group
What happens at point C?
Isoelectric point
What happens at point D?
pKa of amino group
What happens at point E?
Neither amino nor carboxyl groups are protonated
The proteasome consists of two 19S caps and one 20S core, where are the catalytic subunits contained?
Inner surface of the 20s core
The glycine residue of ubiquitin attaches to which amino acid on the target protein?
Lysine
