hemistry 2100 hapter 22
Proteins Proteins serve many functions, including the following. 1. Structure: ollagen and keratin are the chief constituents of skin, bone, hair, and nails. 2. atalysts: Virtually all reactions in living systems are catalyzed by proteins called enzymes. 3. Movement: Muscles are made up of proteins called myosin and actin. 4. Transport: emoglobin transports oxygen from the lungs to cells; other proteins transport molecules across cell membranes. 5. ormones: Many hormones are proteins, among them insulin, oxytocin, and human growth hormone.
Proteins 6. Protection: Blood clotting involves the protein fibrinogen; the body used proteins called antibodies to fight disease. 7. Storage: asein in milk and ovalbumin in eggs store nutrients for newborn infants and birds. Ferritin, a protein in the liver, stores iron. 8. Regulation: ertain proteins not only control the expression of genes, but also control when gene expression takes place. Proteins are divided into two types: Fibrous proteins Globular proteins
2 R nonpolar polar / neutral acidic / basic
hirality of α-amino Acids With the exception of glycine, all proteinderived amino acids have at least one stereocenter (the α-carbon) and are chiral. The vast majority of α-amino acids have the L- configuration at the α-carbon. - 3 + - + 3 3 3 D-Alanine L-Alanine (Fischer projections)
2 R nonpolar polar / neutral acidic / basic
Protein-Derived α-amino Acids onpolar side chains (at p 7.0) 3 + - Alanine (Ala, A) 3 + - Phenylalanine (Phe, F) 3 + - Glycine (Gly, G) - Proline (Pro, P) S 3 + 3 + 3 + - - - Isoleucine (Ile, I) Leucine (Leu, L) Methionine (Met, M) - 3 + 3 + - Tryptophan (Trp, W) Valine (Val, V)
Protein-Derived α-amino Acids Polar side chains (at p 7.0) 2 3 + - Asparagine (Asn, ) S - 3 + ysteine (ys, ) 2 3 + - Glutamine (Gln, Q) - 3 + Serine (Ser, S) - 3 + Tyrosine (Tyr, Y) - 3 + Threonine (Thr, T)
Protein-Derived α-amino Acids Acidic and basic side chains (at p 7.0) - - - 3 + - 3 + Aspartic acid (Asp, D) Glutamic acid (Glu, E) 2 2 + - 3 + - 3 + Arginine (Arg, R) istidine (is, ) + 3-3 + Lysine (Lys, K)
essential amino acids Leu, Ile, Lys, Met, Phe, Thr, Trp, Val, is ( Arg, Tyr, ys )
3 3 + 2-3 2 R R R zwitterion
Ionization vs. p The net charge on an amino acid depends on the p of the solution in which it is dissolved. If we dissolve an amino acid in water, it is present in the aqueous solution as its zwitterion. If we add a strong acid such as l to bring the p of the solution to 0.0, the strong acid donates a proton to the - - of the amino acid turning the zwitterion into a positive ion. + 3 --- - R + 3 + + 3 --- R + 2
Ionization vs. p If we add a strong base such as a to the solution and bring its p to 14, a proton is transferred from the 3 + group to the base turning the zwitterion into a negative ion. + 3 --- - R To summarize: + - 2 --- - R + 2 + 3 --- R - 3 + + 3 --- - R - 3 + 2 --- - R
Problem: alculate the net charge of lysine at p = 3, 7, 11. Estimate pi for lysine. 2 2 2 2 2 2
2 2 2 2 2 2 p = 7
( ) 2 2 2 2 2 2 p = 7
( ) (+) 2 2 2 2 2 2 p = 7
( ) (+) 2 2 2 2 2 2 p = 7 (+)
( ) 2 (+) 2 2 2 2 2 2 2 2 2 2 2 (+) p = 7
( ) 2 (+) 2 2 2 2 2 2 2 2 2 2 2 (+) p = 3 p = 7
( ) (+) 2 (+) 2 (+) (+) 2 2 2 2 2 2 2 2 2 2 p = 3 p = 7
( ) (+) 2 (+) 2 2 (+) (+) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 p = 3 p = 7 p = 11
( ) ( ) (+) 2 (+) 2 2 (+) (+) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 p = 3 p = 7 p = 11
Isoelectric Point (pi) Isoelectric point, pi: The p at which the majority of molecules of a compound in solution have no net charge. onpolar & polar side chains alanine asparagine cysteine glutamine glycine isoleucine leucine methionine phenylalanine proline serine threonine tyrosine tryptophan valine pi 6.01 5.41 5.07 5.65 5.97 6.02 5.98 5.74 5.48 6.48 5.68 5.87 5.66 5.88 5.97 Acidic Side hains aspartic acid glutamic acid Basic Side hains arginine histidine lysine pi 2.77 3.22 pi 10.76 7.59 9.74
Problem: Predict the electrophoresis behavior at p 6.0 of a mixture of alanine (pi 6.0), aspartic acid (pi 2.8) and lysine (pi 9.7)
Problem: Predict the electrophoresis behavior at p 6.0 of a mixture of alanine (pi 6.0), aspartic acid (pi 2.8) and lysine (pi 9.7)
Problem: Predict the electrophoresis behavior at p 6.0 of a mixture of alanine (pi 6.0), aspartic acid (pi 2.8) and lysine (pi 9.7)
Problem: Predict the electrophoresis behavior at p 6.0 of a mixture of alanine (pi 6.0), aspartic acid (pi 2.8) and lysine (pi 9.7) Lys Ala Asp
Peptide Bonds 2 + 2 (-) 2 R R' R R'
Peptide Bonds 2 + 2 (-) 2 R R' R R'
Peptide Bonds 2 + 2 (-) 2 R R' R R'
Peptide Bonds 2 + 2 (-) 2 R R' R R'
Peptide Bonds 2 + 2 (-) 2 R R' R R'
R' R" α α α α α R R" R" "
R' R" α α α α α R R" R" "
R' R" α α α α α R R" R" "
R' R" α α α α α R R" R" "
R' R" α α α α α R R" R" "
(-terminus) (+) 2 (+) ( ) ( 2 ) 4 2 2 2 2 S 3 2 ( 2 ) 3 2 lysylserylmethionylaspartylarginine [Lys Ser Met Asp Arg] (-terminus) (+) ( )
(-terminus) (+) 2 (+) ( ) ( 2 ) 4 2 2 2 2 S 3 2 ( 2 ) 3 2 lysylserylmethionylaspartylarginine [Lys Ser Met Asp Arg] (-terminus) (+) ( )
(-terminus) (+) 2 (+) ( ) ( 2 ) 4 2 2 2 2 S 3 2 ( 2 ) 3 2 lysylserylmethionylaspartylarginine [Lys Ser Met Asp Arg] (-terminus) (+) ( )
(-terminus) (+) 2 (+) ( ) ( 2 ) 4 2 2 2 2 S 3 2 ( 2 ) 3 2 lysylserylmethionylaspartylarginine [Lys Ser Met Asp Arg] (-terminus) (+) ( )
(-terminus) (+) 2 (+) ( ) ( 2 ) 4 2 2 2 2 S 3 2 ( 2 ) 3 2 lysylserylmethionylaspartylarginine [Lys Ser Met Asp Arg] (-terminus) (+) ( )
(-terminus) 2 ( ) ( 2 ) 4 2 2 2 2 S 3 2 ( 2 ) 3 2 lysylserylmethionylaspartylarginine [Lys Ser Met Asp Arg] (-terminus) ( ) p = 7
(-terminus) (+) 2 (+) ( ) ( 2 ) 4 2 2 2 2 S 3 2 ( 2 ) 3 2 lysylserylmethionylaspartylarginine [Lys Ser Met Asp Arg] (-terminus) (+) ( ) p = 7
(-terminus) (+) 2 (+) ( ) ( 2 ) 4 2 2 2 2 S 3 2 ( 2 ) 3 2 lysylserylmethionylaspartylarginine [Lys Ser Met Asp Arg] (-terminus) (+) ( ) p = 3
(-terminus) (+) 2 (+) ( ) ( 2 ) 4 2 2 2 2 S 3 2 ( 2 ) 3 2 lysylserylmethionylaspartylarginine [Lys Ser Met Asp Arg] (-terminus) (+) ( ) p = 3
(-terminus) 2 ( ) ( 2 ) 4 2 2 2 2 S 3 2 ( 2 ) 3 2 lysylserylmethionylaspartylarginine [Lys Ser Met Asp Arg] (-terminus) ( ) p = 11
(-terminus) 2 ( ) ( 2 ) 4 2 2 2 2 S 3 2 ( 2 ) 3 2 lysylserylmethionylaspartylarginine [Lys Ser Met Asp Arg] (-terminus) ( ) p = 11
Lys œ Ser œ Met œ Asp œ Arg 2 + + + + + or - Arg Asp Lys Met Ser (5!) = 120 combinations (20!) = 2.4 10 18 eicosapeptides (20 5 ) = 3.2 10 6 possible pentapeptide
Lys œ Ser œ Met œ Asp œ Arg 2 + + + + + or - Arg Asp Lys Met Ser (5!) = 120 combinations (20!) = 2.4 10 18 eicosapeptides (20 5 ) = 3.2 10 6 possible pentapeptide
Lys œ Ser œ Met œ Asp œ Arg 2 + + + + + or - Arg Asp Lys Met Ser (5!) = 120 combinations (20!) = 2.4 10 18 eicosapeptides (20 5 ) = 3.2 10 6 possible pentapeptide
Lys œ Ser œ Met œ Asp œ Arg 2 + + + + + or - Arg Asp Lys Met Ser (5!) = 120 combinations (20!) = 2.4 10 18 eicosapeptides (20 5 ) = 3.2 10 6 possible pentapeptide
Lys œ Ser œ Met œ Asp œ Arg 2 + + + + + or - Arg Asp Lys Met Ser (5!) = 120 combinations (20!) = 2.4 10 18 eicosapeptides (20 5 ) = 3.2 10 6 possible pentapeptide
Lys œ Ser œ Met œ Asp œ Arg 2 + + + + + or - Arg Asp Lys Met Ser (5!) = 120 combinations (20!) = 2.4 10 18 eicosapeptides (20 5 ) = 3.2 10 6 possible pentapeptides
S S 2 ys ys Pro Leu Gly 2 Tyr Ile Gln Asn oxytocin S S 2 ys ys Pro Arg Gly 2 Tyr Phe Gln Asn vasopressin
Enkephalins 3 Morphine 2 2 3 2 3 Tyr Gly Gly Phe Met Tyr Gly Gly Phe Leu Methionine Leucine enkephalin
Insulin S S 5 10 15 20 Gly Ile Val Glu Gln ys ys Thr Ser Ile ys Ser Leu Tyr Gln Leu Glu Asn Tyr ys Asn S S S 5 10 15 20 25 30 Phe Val Asn Gln is Leu ys Gly Ser is Leu Val Glu Ala Leu Tyr Leu Val ys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Thr S
Structure of Proteins
R R' R" R" R" " R
R R' R" R" R" " R
R R' R" R" R" " R
R R' R" R" R" " R
Secondary Structure: The α-elix
β-pleated Sheet
Random oil
β-pleated sheet α-helix α-helix β-pleated sheet
Protein Tertiary Structure
β-pleated sheet α-helix α-helix β-pleated sheet
β-pleated sheet α-helix salt bridge - 3 + α-helix β-pleated sheet
β-pleated sheet α-helix salt bridge - 3 + α-helix 2 hydrogen bond 2 β-pleated sheet
β-pleated sheet α-helix hydrogen bond salt bridge - 3 + α-helix 2 hydrogen bond 2 β-pleated sheet
hydrophilic interaction to water β-pleated sheet α-helix 2 2 2 hydrogen bond 2 salt bridge - 3 + α-helix 2 hydrogen bond 2 β-pleated sheet
hydrophilic interaction to water β-pleated sheet α-helix 2 2 2 2 2 hydrogen bond hydrophobic interaction 2 salt bridge - 3 + α-helix 2 hydrogen bond 2 β-pleated sheet
hydrophilic interaction to water β-pleated sheet α-helix 2 2 2 2 2 hydrogen bond hydrophobic interaction 3 3 3 2 salt bridge - 3 + α-helix 2 hydrogen bond 2 β-pleated sheet
hydrophilic interaction to water β-pleated sheet α-helix 2 2 2 2 2 hydrogen bond hydrophobic interaction 3 3 3 2 salt bridge - 3 + S S disulfide bond S S α-helix 2 hydrogen bond 2 β-pleated sheet
Protein Quaternary Structure
emoglobin 3032 4816 735 780 S 8 Fe 4 (MW 64,450)
Sickle-ell Anemia
Sequence Varies: Ask 23andMe
Proteins
Denaturation
Denaturation also known as ooking
Misfolding Diseases
Mutation Impairs Proper Folding ystic Fibrosis Sickle ell Anemia
ontagious Misfolding: Prions