Amino Acids Flashcards
Increasing Hydrophobicity
Larger chains of CH3= greater hydrophobicity (more carbon hydrogen chains will repel water better)
Aromatic Groups= less or no hydroxyl groups means more hydrophobic
Disulfide Bridge
Cysteine form Sulfur-Sulfur bonds.
Ex: Inside insulin
Cys—-S–S——Cys
Positively Charged R groups
Histidine, Lysine, and Arginine.
Lysine and Arginine will bring their positive
Basic?
Polar and Negatively Charged
Aspartate and Glutamate
Essential Amino Acids
Arganine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylaline, Threonine, Tryptophan, Valine
10 essential amino acids.
Scurvy
Rich in collagen.
Lacking in Hydroxyrproline.
Y- carboxyglutumate
Present in several blood clotting factors.
Vitamin K deficiency= Warfarin
Glycosylation
O linked glycosylation: Sugars added to Ser or Thr
N linked glycosylation: Sugars added to the asparagine in the
sequences -X-N-X-S/T-
Gleevec
a bcr-abl tyrosine kinase inhibitor used to treat chronic myelogenous leukemia (CML)
Peptide bond and peptide plane
Rotation around the peptide bond not permitted
Rotation around ψ and φ (dihedral angles) permitted
φ (phi): angle around the C—amide nitrogen bond
ψ (psi): angle around the C—carbonyl carbon bond
In a fully extended polypeptide, ψ and φ are 180°
Secondary structures: a local spatial arrangement of the polypeptide chain
Alpha Helices: 30%
Beta Pleated Sheets: 30%
Turns and Loops Triple Helix (as seen in collagen)
α-helix
H-bonds between backbone carbonyl (CO) and amine (NH) within a polypeptide chain forms the α-helix
A right -handed screw
H-bonds between CO of residue n and the NH of residue n+4
Ex: Leucine zipper
Small hydrophobic residues such as Ala and Leu are strong helix formers
Pro and Gly are helix breakers
Structural fibrous proteins Keratin-hair, nails, horns
Myosin
Tropomyosin
fibrinogen
Globular: Hemoglobin, Myoglobin
Beta Sheets
The backbone is more extended
Has a pleated sheet-like structure
Hydrogen bonds between the backbone of neighboring strands
Side chains protrude from the sheet alternating in up and down direction
Secondary Structure: β Turns
β-turns occur frequently whenever strands in β sheets change the direction
The 180° turn is accomplished over four amino acids
The turn is stabilized by a hydrogen bond from the carbonyl oxygen of the 1st amino acid to amide proton of the 4th amino acid
Proline in position 2 or glycine in position 3 are common in β-turns
four amino acids turn
- hydrogen bond between the 1st and the 4th amino acid
- Proline in position 2 or glycine in position 3 are common
Proline Isomers
Most peptide bonds are in the trans configuration
For peptide bonds involving proline, ~6% are in the cis configuration.
Proline isomerization is catalyzed by prolyl isomerases
Protein Tertiary Structure
-overall spatial arrangement of atoms in a polypeptide chain or in a protein
-Two major classes
fibrous proteins
¤ typically insoluble; made from a single secondary structure
globular proteins
water-soluble globular proteins
lipid-soluble membraneous proteins
Motifs (folds)
Domains
Arrangements of several secondary structure elements
Many proteins are made up of multiple stable globular units called domains. Domains have more-or-less independent functions.
Quaternary Structure
Quaternary structure is formed by multiple polypeptides into a larger functional cluster
Structure of Collagen
Collagen is an important constituent of connective tissue: tendons, cartilage, bones, cornea of the eye
Each collagen chain is a long Gly- and Pro-rich left-handed helix
Three collagen chains intertwine into a right-handed superhelical triple helix
The triple helix has higher tensile strength than a steel wire of equal cross section
Structure and functions of Globular Proteins
Storage of ions and molecules -myoglobin, ferritin Transport of ions and molecules -hemoglobin, serotonin transporter Defense against pathogens -antibodies, cytokines Muscle contraction -actin, myosin Biological catalysis -chymotrypsin, lysozyme
Function of Myoglobin
Need to store oxygen for metabolism
Protein side-chains lack affinity for O2
Some transition metals bind O2 well but would generate free radicals if free in solution
Organometallic compounds such as heme are more suitable but Fe2+ in free heme could be irreversibly oxidized to Fe3+ which no longer binds oxygen
Solution:
Bury heme and bound oxygen inside the protein
In mammals, myoglobin is the main oxygen storage protein
Hemoglobin and cooperativity
Must be a protein with multiple binding sites
Binding sites must be able to interact with each other
This phenomenon is called allostery or cooperativity
positive cooperativity: first binding event increases affinity at remaining sites
negative cooperativity: first binding event reduces affinity at remaining sites
Hemoglobin is a tetramer of two subunits (α2β2)
Each subunit is similar to myoglobin
The four subunits interact with each other
Blood in lungs has higher pH than blood in metabolic tissues
Affinity for oxygen depends on the pH
Oxygen binds well at higher pH
Oxygen is released well at lower pH
The pH difference between lungs and metabolic tissues increases the O2 transfer efficiency
This is known as the Bohr effect
Hemoglobin also Transports H+ and CO2
CO2 is produced by metabolism in tissues and must be exported
Some CO2 exported as dissolved bicarbonate in the blood
Some CO2 is exported in the form of a carbamate on the amino terminal residues of each of the hemoglobin subunits.
Protein Structure Methods:
X-Ray Crystallography
Steps needed: Purify the protein Crystallize the protein Collect diffraction data Calculate electron density Fit residues into density
Pros:
No size limits
Cons:
Crystallization is the rate-limiting step
Structure Methods:
Biomolecular NMR
Steps needed: Purify the protein Dissolve the protein Collect NMR data Assign NMR signals Calculate the structure
Pros:
No need to crystallize the protein
Cons:
Need very concentrated proteins
Very difficult for large proteins (
The first class of chaperones: Hsp70/Hsp40
prokaryotic homologs: DnaK and DnaJ
induced at elevated temperatures
bind to hydrophobic region of unfolded protein and prevent aggregation
help transport some proteins cross membranes in unfolded states
Some protein folding pathways require protein disulfide isomerase (PDI)
Secreted or cell surface proteins.
The correct disulfide bonds often do not form on their own in proteins with many free cysteines.
Protein disulfide isomerase reduces improper disulfide bonds and reform them correctly.
