Lecture 4: Structure and Proteins- AA Flashcards
Hydrophobic AA’s
Glycine Alanine Proline Valine Leucine Isoleucine Methionine Tryptophan Phenylalanine
Polar AA’s
Serine Threonine Asparagine (Asn) - N Gluatamine (Gln) - Q Cysteine
Charged (+) AA’s
Lysine
Arginine (Arg) - R
Histidine
Charged (-) AA’s
Aspartate (Asp) - D
Glutamate (Glu) - E
pKa’s of Ionizing Side Chain
Arginine (12.5) Aspartic Acid (4.1) Cysteine (8.3) Glutamic acid (4.1) Histidine (6.0) Lysine (10.8) Tyrosine (10.9)
Tiny AA’s
A, G, C, S
Small AA’s
P, T, D, N
Medium AA’s
V, E, H, Q
Large AA’s
I, L, K, R, M
Very Large
Y, F, W
Essential AA’s
[Humans cannot synthesize]:
H, I, L, K, F, T, W, V
[Consumption>Production]:
R, M
Non-essential AA’s
[Humans can synthesize de novo]:
D, A, N, C, Q, E, G, P, S
[Secondary synthesis]:
Y
Essential AA’s (mnemonic)
P - phenylalanine
V - Valine
T - Tryptophan
T - Threonine
I - Isoleucine
M - Methionine
H - Histidine
A - Arginine
L - Lysine
L - Leucine
Selenocysteine (Sec, U) - 21st AA
- pKa= 5.2
- Synthesized from Serine
- Processed to selenomethionine in plants, algae, and yeast; Alanine in animals
- 21st AA
Stop codons
UGA, UAA, UAG
Selenocysteine (Sec, U) and uses of UGA (opal)
-Within mitochondria, UGA = W codon
-In some ciliates, UGA = C codon
-Found in ALL 3 domains of life
-Uses own tRNA and SECIS
[Selenocysteine Insertion]
Selenoproteins
Proteins that incorporate Secs
Why are selenoproteins important for good health?
- Reduce oxidative stresses in conjunction with Vitamine E
- Required in cerebellum neurons (growth and coordination)
- Moderate inflammatory responses - can reduce IBS
Selenium deficiences result in
- Myopathies (Keshan disease- cardiomyopathy and Statin intolerance- rhabdomyolysis)
- Immune-incompetence
Keshan disease (Cardiomyopathy)
[Myopathy]
- Caused by not enough selenium in diet
- Oxidative stress is disinhibited
- Treated with Se supplements
Statin-intolerance (Rhabdomyolysis)
- Statins inhibit Sec-tRNA
- Treated by discontinuing statin
Statins
Block formation of cholesterol in the liver
Too much Selenium
- Hair and nail brittleness (Garlic breath)
- GI/Neuro lesions
- Myopathies, renal failure, and death
Pyrrolysine (Pyl, O)
- Made by combining 2 lysisines
- Found only in some prokaryotes, all are methanogens
- Uses own tRNA
- Named 22nd AA
Pyrrolysine (Pyl, O) and uses of UAG (amber)
- Usually UAG and UAA are reprogrammed togetherr
- UAG can also be an L or Q codon in some organisms
Pyrrolysine - human intestinal microbe make/use Pyl
- Methanomassiliicoccus luminyensis (Archae)
2. Bilophila wadsorthia (Euchbacteria)
Methanomassiliicoccus luminyensis (Archaea)
-Methanogen, Gram-neg, non-motile, coccoid
Bilophila wadsorthia (Euchbacteria)
- Opportunistic pathogen, Gram-neg, anaerobic, rod
- Penicillin-resistant
- Common in gangrenous and abscessed tissues/organs
- Overabundance may be linked to IBD/colitis
- In mice, fish oil (unsat fats) decreases blooms but lard/milk fats (sat fats) increases blooms
Non-proteinogenic AA’s
- Post-translational additions to proteinogenic AA’s (Addition of phosphate grp)
- D-entantiomers (bacterial peptidoglycan walls often contain D-Ala and D-glu)
- Metabolism intermediates (ornithine and citrulline in the urea cycle)
- Pre-biotic or extraterrestrial origin (Rudimentary AA’s that did not make it into the genetic code, like alpha, gamma-diaminobutyric acid (DAB)
NRPS (Non-ribosomal protein synthesis)
NRPS can make proteins and ANTIBIOTICS
- A/Adenylation- activate carboxyl
- PCP/Peptidyl Carrier Protein (T/Thiolation) - elongation intermediate
- C/Condensation- peptide bond formation
- TE/Thioesterase - release or cyclization
Antibiotics are made by
NRPS !!! First Abx= B-lactams like pencillin An AVC tripeptide= L-alpha-aminoadipate-L-Cys-D-Val Newest class of Abx= Odilorhabdins (Lys- DAB (BOH)-DAB (BOH)- Gly-Orn-Pro-His -Dhl-Dha-Dhl-Dbt)
Statins are made by
Polyketide synthesis (PKS)
Primary structure
A linear chain of AA’s
Secondary structure
Local folding of the polypeptide chain, connected by Hydrogen bonds; Repetitive arrangements of amino acids that are near each other in the linear sequence
Tertiary structure
Folding of the secondary structure, connected by disulfide linkages; Overall folding of a single polypeptide chain, which can include α-helical and/or β-sheet structures
Quaternary structure
Interaction of multiple peptides; Association of at least 2 protein subunits
Single bonds means
Rotation is possible (cis and trans)
Peptide bond exists between
Carboxyl carbon (attached to double bonded O) and NH (in amine)
