Biochem Flashcards
WhatWhat two factors entirely determine the individual function of proteins?
Length of polymer and amino acid sequence
What is a typical psi angle for alpha helices?
Around zero degrees for alpha helices, and around 180 for beta sheets
Which bond axis is used for phi angles?
The N-Ca bond
What are the four types of interactions of proteins?
- Electrostatic
- hydrogen bonding
- Van der Waals
- Hydrophobic (most important)
Explain the hydrophobic effect
The fact that H2O has an unusually high attraction for itself due to the ability to hydrogen bond with itself, this causes the formation of clathrates which are highly ordered structures surrounding collections of hydrophobic molecules. Although this decreases entropy, thus energetically unfavorable, you get a net bonus of energy by walling off the hydrophobic molecules
What is the most frequently observed secondary protein structure?
alpha helix: every atom of the 4th amino acid is the closest together in the structure, hydrogen bonding helps stabilize it, side chains tilt back towards N-terminus
Does the geometry of a hydrogen bond matter?
yes linear bonds are strongest
What are the main helix breakers?
Strong: proline, glycine
Medium: Beta branched or bulky
Indifferent: long, straight chains
What type of periodicity does a beta sheet have?
A periodicity of 2 meaning hydrophilic-hydrophobic repeats
What is required and what is preferred in a beta turn?
A glycine is usually required and a proline is preferred to provide a kink
What are motifs?
Short stretches of secondary structure which are typically not stable by themselves and are surrounded by support structures
What is a Helix Turn Helix motif?
It is a type of motif consisting of two alpha helices joined by a short strand of amino acids capable of binding DNA. An alpha helix fits well into the major groove of DNA which will H-bond to the Watson/Crick base pairs
What is characteristic of zinc finger nucleases?
In order to bind DNA they typically have cysteine and histidine residues spaced in a helical pattern (i+3/4)
What is the signature sequence of coiled coil?
A heptad repeat (positions a-g)
of the same types of amino acids
They are extremely stable
(a and d)nonpolar
(e and g) oppositely charged
Found in transciption factors (GCN4)
What is different between HA and the gp120/gp441 complex?
Hemmaglutenin (HA) is triggered by a pH change
gp120/gp41 is triggered by a receptor binding
What is the function of Hsp60 and Hsp70
Chaperones which prevent aggregation during folding
Note: most proteins do not require chaperones
How is ATP involved in the ubiquitin-proteasome pathway?
It is required to bind the first ubiquitin and the 26S proteasome requires ATP for its catlytic activity
What’s the role of E/1/2/3 in the ubiquitin proteasome pathway?
E1: activates ubiquitin (ATP driven)
E2: Transfers ubiquitin to target protein
E3: catalyzes transfer to the amino group of lysine
Which domain is primarily affected in p53 mutations?
DNA binding domain
What is MDM2?
An E3 ubiquitin ligase that recognizes p53
Which delection is the cause of 70% of cystic fibrosis?
Phe508 aka deltaF508
(the three codons which encoded for phenylalanine were deleted from the gene)
This amino acid exists on the surface of a nucleotide binding domain
This deletion imposes effects on the folding pathway of the CFTR
What is alpha AT deficiency?
alpha AT (antitrypsin) is a serine protease inhibitor it works by a mousetrap mechanism (serpin) deficiency: causes empysema and liver disease it results from unchecked nutrophil elastase (a serine protease which facilitates movement of inflammoratory cells)
Caused by one of two point mutations
What is the effect of RCL (reactive center loop) misfiring in the liver from alpha AT mutations?
Accumulations of the protein aggregates build up and eventually cause liver failure.
What is a common theme to prion accumulation models?
Beta sheets
What amyloid precursor product is related to Alzheimer’s Disease?
ABeta42
What is the pKa of Asp/Glu
pH=4
What is the pKa of the amino and carboxyl ends of an amino acid?
Amino: pH 8.0
Carboxyl: pH 4.0
How does proline facilitate beta turns?
Because of its unique structure X-Pro can exist in the cis position about 1/4th of the time
What is the pKa of Histidine?
pH 6.5
What is the pKa of Lys?
pH 10.0
What is the pKa of Arginine?
pH 12.0
What is the pKa of Cysteine
pH 8.5
Which organ is effected by alpha 1 antitrypsin deficiency?
Primarily the lungs which can lead to emphysema
also liver (cirrhosis)
What does serpin stand for?
Serine Protease Inhibitor
where is alpha 1 antitrypsin synthesized?
In the liver which is why it can be so severely negatively effected
Does the RCL (reactive center loop) beta sheet need to be inserted into itself?
No, it can insert into it’s identical neighbors as well especially in the event of misfiring. This can rapidly cause aggregates in the liver leading to liver failure.
