AA peptides, and proteins Flashcards
non-polar aliphatic AA
Glycine, alanine, valine, leucine, methionine, isoleucine
polar uncharged AA
syrine, threonine, cysteine, proline, asparagine, glutamine
positively charged AA
lysine, arginine, histidine
negatively charged AA
aspartate, glutamate
non-polar aromatic AA
phenylalanine, tyrosine, tryptophan
Describe the function of disulphide bonds within proteins
Important for tertiary structure of proteins, adding stability and changes in shape to proteins.
Describe the major post‐translational covalent modifications of amino acid side chains in proteins and identify the post-translational modification targeted by the disease process or medicine discussed in class; hydroxylation
Hyrdroxylation: Hydropxyproline: hydroxyl group added. Important in collagen structure where L handed helixes are stabilized by H bonds with this. Scurvy: enzyme hydroxylating proline needs vitamin c to act
Describe the major post‐translational covalent modifications of amino acid side chains in proteins and identify the post-translational modification targeted by the disease process or medicine discussed in class; Carboxylation
Carboxylation: Carboxyglutamate: addition of carboxyl group to glutamate. Necessary in certain clotting factors. Warfarin inhibits enzyme function. Vitamin k deficiency: enzyme needs K to add carboxyl group to glutamate, results in insufficient clotting
Describe the major post‐translational covalent modifications of amino acid side chains in proteins and identify the post-translational modification targeted by the disease process or medicine discussed in class; glycosylation
O linked: Ser and Thr N linked: Asparagine If mutated: congenital disorder of glycosylation, leads to severe or fatal disorder involving nervous system, muscle, instestines
Describe the major post‐translational covalent modifications of amino acid side chains in proteins and identify the post-translational modification targeted by the disease process or medicine discussed in class; Acetylation or Methyaltion
Lys: can be acetylated or methylated Drugs: Vorinostat or HDAC Arg: can be methylated Important in chromatin remodeling, HATS will acetylate, negate positive charge
Describe the major post‐translational covalent modifications of amino acid side chains in proteins and identify the post-translational modification targeted by the disease process or medicine discussed in class; Acetylation or Methyaltion
Lys: can be acetylated or methylated Drugs: Vorinostat or HDAC Arg: can be methylated Important in chromatin remodeling, HATS will acetylate, negate positive charge
Describe the major post‐translational covalent modifications of amino acid side chains in proteins and identify the post-translational modification targeted by the disease process or medicine discussed in class; Reversible phosphorylation
Ser, Thr, Tyr can be reversibly phosphorylated CML (leukemia) patients have fusion protein which causes kinase to be constantly active, constant proliferation Drug, geelvec, competitively bind and inhibits overactive protein
Describe the major post‐translational covalent modifications of amino acid side chains in proteins and identify the post-translational modification targeted by the disease process or medicine discussed in class; ubiquitination
- Normally ubq marks cells for proteasome destruction - Drug: bortezomib (Velcade) acts to prevent ubiquitination, thus inhibiting cells ability to degrade protein, accumulation of protein occurs and results in cell death
Distinguish three covalent bonds including the peptide bonds that make the backbone of a polypeptide chain.
φ (phi): angle around the C—amide nitrogen bond ψ (psi): angle around the C—carbonyl carbon bond Peptide bond itself cannot rotate due to partial double bond
Distinguish that the amino acid sequence determines the function; mutations in amino acid sequence can cause genetic disease (give example)
Sickle cell anemia; caused by single AA change (glutamate to valine)
Recognize that proteases and the specific breaking of peptide bonds can have important functions.
Proteases can either digest any protein (digestion) or specific proteins at specific peptide bonds. Certain proteins need to be cleaved in order to fold correctly and become functional Ex) Thrombin and clotting cascade
Describe hydrogen bonds and their role in secondary structure formation.
H bonds form between multiple R groups, the NH backbone, and the O backbone In alpha helix, have H bonding between backbone NH and O, occurring every 4 AA In beta sheets, have H bonding between H bonds in neighboring sheets.
Describe secondary structure alpha helix
R handed helix that is very tight (nothing can fit within it) H bonds within backbone every 4 AA Bind well within major groove DNA Residues 1 and 8 fit nicely overtop each other
Describe secondary structure Beta sheet
Pleated sheet like structure H bonds between backbone of neighboring strand Side chains protrude alternating up and down Can be parallel or antiparallel (antiparallel more stable)
Explain tertiary structures
Overall spatial arrangement of atoms in protein. Two major types: Fibrous proteins: Single secondary structure, insoluble Globular proteins: Multiple secondary structures, water and lipid soluble
Explain quaternary structures
Multiple separate tertiary structures coming together to form single protein (hemoglobin)
Explain the role of loops in protein structure and function.
Certain amino acids unable to form secondary structure, loops instead form (gly and pro) Leads to differential folding Differential function, ie immunoglobulin variable domains, collagen
Explain how to use Kd to represent binding strength.
Kd represents the amount of ligand needed to bind half of a certain protein. Lower the Kd, the higher affinity the ligand has for a protein
Explain how binding specificity can be achieved
Lock and Key Protein binding site and ligand are complementary in size, shape, charge, hydrophobic/philic character. fit together like lock and key. Induced fit Upon first ligand binding, a conformational change occurs in protein that increases its affinity for another ligand
