Chemistry 2100 Lecture 10. Proteins Proteins serve many functions, including the following....
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Transcript of Chemistry 2100 Lecture 10. Proteins Proteins serve many functions, including the following....
Chemistry 2100
Lecture 10
ProteinsProteins serve many functions, including the following.– 1. Structure:Structure: Collagen and keratin are the chief
constituents of skin, bone, hair, and nails.– 2. Catalysts:Catalysts: Virtually all reactions in living systems
are catalyzed by proteins called enzymes.– 3. Movement:Movement: Muscles are made up of proteins
called myosin and actin.– 4. TransportTransport: Hemoglobin transports oxygen from
the lungs to cells; other proteins transport molecules across cell membranes.
– 5. Hormones:Hormones: Many hormones are proteins, among them insulin, oxytocin, and human growth hormone.
Proteins– 6. Protection: Protection: Blood clotting involves the protein
fibrinogen; the body used proteins called antibodies to fight disease.
– 7. Storage:Storage: Casein in milk and ovalbumin in eggs store nutrients for newborn infants and birds. Ferritin, a protein in the liver, stores iron.
– 8. Regulation:Regulation: Certain 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
• nonpolar
• polar / neutral
• acidic / basic
COOH
R
HH2 N
Chirality of -Amino AcidsWith the exception of glycine, all protein-derived amino acids have at least one stereocenter (the -carbon) and are chiral.– The vast majority of -amino acids have
the L-configuration at the -carbon.
H NH3+
COO-
CH3
+H3N H
COO-
CH3
D-Alanine L-Alanine
(Fischer projections)
• nonpolar
• polar / neutral
• acidic / basic
COOH
R
HH2 N
Protein-Derived -Amino Acids
Nonpolar side chains (at pH 7.0)
NH3+
COO-
NH3+
COO-
NH3+
COO-
NH3+
COO-
NH3+
COO-S
NH3+
COO-
NH H
COO-
NH3+
COO-
NH
COO-
NH3+
Alanine (Ala, A)
Glycine (Gly, G)
Isoleucine (Ile, I)
Leucine (Leu, L)
Methionine (Met, M)
Phenylalanine (Phe, F)
Proline (Pro, P)
Tryptophan (Trp, W)
Valine (Val, V)
Protein-Derived -Amino Acids
• Polar side chains (at pH 7.0)
NH3+
COO-
HS
NH3+
COO-
HO
Cysteine (Cys, C)
Tyrosine (Tyr, Y)
NH3+
COO-H2N
O
NH3+
COO-
H2N
O
NH3+
COO-
HO
NH3+
COO-OH
Asparagine (Asn, N)
Glutamine (Gln, Q)
Serine (Ser, S)
Threonine (Thr, T)
Acidic and basic side chains (at pH 7.0)
Protein-Derived -Amino Acids
NH3+
COO--O
O
NH3+
COO--O
O NH3+
COO-
NH
H2N
NH2+
NH3+
COO-
N
NH
NH3+
COO-H3N
Glutamic acid (Glu, E)
Aspartic acid (Asp, D)
Histidine (His, H)
Lysine (Lys, K)
Arginine (Arg, R)
+
essential amino acids
Leu, Ile, Lys, Met, Phe, Thr, Trp, Val, His ( Arg, Tyr, Cys )
zwitterion
H2 N H
COO
R
H2 N H
COOH
R
H3 N H
COOH
R
H3O+
OH-
H3
Ionization vs. pH
The net charge on an amino acid depends on the pH 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 HCl to bring the pH of the solution to 0.0, the strong acid donates a proton to the -COO- of the amino acid turning the zwitterion into a positive ion.
+
RH3N-CH-C-O
-O
+ H3O+ +
RH3N-CH-C-OH
O+H2O
Ionization vs. pH
– If we add a strong base such as NaOH to the solution and bring its pH to 14, a proton is transferred from the NH3
+ group to the base turning the zwitterion into a negative ion.
– To summarize:
+
RH3N-CH-C-O
-O
+ OH-
RH2N-CH-C-O-
O+H2O
+
RH3N-CH-C-O
-O+
RH3N-CH-C-OH
O
RH2N-CH-C-O-
OOH-
H3O+
OH-
H3O+
Problem: Calculate the net charge of lysine at pH = 3, 7, 11. Estimate pI for lysine.
CH2CH2CH2CH2NH2
H2N H
COOH
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 7
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 7
(–)
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 7
(–)
(+)
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 7
(–)
(+)
(+)
CH2CH2CH2CH2NH2
H2N H
COOH
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 7
(–)
(+)
(+)
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 3
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 7
(–)
(+)
(+)
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 3
(+)
(+)
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 7
(–)
(+)
(+)
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 11
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 3
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 7
(–)
(+)
(+)
(+)
(+)
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 11
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 3
CH2CH2CH2CH2NH2
H2N H
COOH
pH = 7
(–)
(+)
(+)
(+)
(+)
(–)
Isoelectric Point (pI)• Isoelectric Isoelectric
point, pI:point, pI:The pH at which the majority of molecules of a compound in solution have no net charge.
6.015.41
5.655.976.025.985.745.486.485.685.87
5.885.97
pI
valinetryptophan
threonineserineprolinephenylalaninemethionineleucineisoleucineglycineglutamine
asparaginealanine
Nonpolar &polar side chains
10.76
2.77
5.073.22
7.599.74
5.66
pI
tyrosine
lysinehistidine
glutamic acidcysteine
aspartic acid
arginine
AcidicSide Chains
BasicSide Chains pI
Problem: Predict the electrophoresis behavior at pH 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 pH 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 pH 6.0 of a mixture of alanine (pI 6.0), aspartic acid (pI 2.8) and lysine (pI 9.7)
Lys Ala Asp
Problem: Predict the electrophoresis behavior at pH 6.0 of a mixture of alanine (pI 6.0), aspartic acid (pI 2.8) and lysine (pI 9.7)
O
OHCH CH2 N
R
O
OHCH CH2 N
R'
+
O
CH CH2N
R R'
NH CCH OH
O(-HOH)
Peptide Bonds
O
OHCH CH2 N
R
O
OHCH CH2 N
R'
+
O
CH CH2N
R R'
NH CCH OH
O(-HOH)
Peptide Bonds
O
OHCH CH2 N
R
O
OHCH CH2 N
R'
+
O
CH CH2N
R R'
NH CCH OH
O(-HOH)
Peptide Bonds
O
OHCH CH2 N
R
O
OHCH CH2 N
R'
+
O
CH CH2N
R R'
NH CCH OH
O(-HOH)
Peptide Bonds
O
OHCH CH2 N
R
O
OHCH CH2 N
R'
+
O
CH CH2N
R R'
NH CCH OH
O(-HOH)
Peptide Bonds
"
"
"
CC
O
H
R
H
R'
H "R
H
"R
H
R H
H
H O
HO
O
OH
NC
CN
CC
NC
CN
CC
N
"
"
"
CC
O
H
R
H
R'
H "R
H
"R
H
R H
H
H O
HO
O
OH
NC
CN
CC
NC
CN
CC
N
"
"
"
CC
O
H
R
H
R'
H "R
H
"R
H
R H
H
H O
HO
O
OH
NC
CN
CC
NC
CN
CC
N
"
"
"
CC
O
H
R
H
R'
H "R
H
"R
H
R H
H
H O
HO
O
OH
NC
CN
CC
NC
CN
CC
N
"
"
"
CC
O
H
R
H
R'
H "R
H
"R
H
R H
H
H O
HO
O
OH
NC
CN
CC
NC
CN
CC
N
O
CH C NH CCH
O
NH
CH2 COOH
NH CCH
O
CH2 OH CH2 CH2 SCH3
O
NHCCHH2 N
(CH2 )4 NH2
CH C OH
O
(CH2 )3 NHCNH2
NHlysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
(–)
(–)
(N-terminus) (C-terminus)
(+)
(+)
(+)
O
CH C NH CCH
O
NH
CH2 COOH
NH CCH
O
CH2 OH CH2 CH2 SCH3
O
NHCCHH2 N
(CH2 )4 NH2
CH C OH
O
(CH2 )3 NHCNH2
NHlysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
(–)
(–)
(N-terminus) (C-terminus)
(+)
(+)
(+)
O
CH C NH CCH
O
NH
CH2 COOH
NH CCH
O
CH2 OH CH2 CH2 SCH3
O
NHCCHH2 N
(CH2 )4 NH2
CH C OH
O
(CH2 )3 NHCNH2
NHlysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
(–)
(–)
(N-terminus) (C-terminus)
(+)
(+)
(+)
O
CH C NH CCH
O
NH
CH2 COOH
NH CCH
O
CH2 OH CH2 CH2 SCH3
O
NHCCHH2 N
(CH2 )4 NH2
CH C OH
O
(CH2 )3 NHCNH2
NHlysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
(–)
(–)
(N-terminus) (C-terminus)
(+)
(+)
(+)
O
CH C NH CCH
O
NH
CH2 COOH
NH CCH
O
CH2 OH CH2 CH2 SCH3
O
NHCCHH2 N
(CH2 )4 NH2
CH C OH
O
(CH2 )3 NHCNH2
NHlysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
(–)
(–)
(N-terminus) (C-terminus)
(+)
(+)
(+)
O
CH C NH CCH
O
NH
CH2 COOH
NH CCH
O
CH2 OH CH2 CH2 SCH3
O
NHCCHH2 N
(CH2 )4 NH2
CH C OH
O
(CH2 )3 NHCNH2
NH
pH = 7
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
(–)
(–)
(N-terminus) (C-terminus)
O
CH C NH CCH
O
NH
CH2 COOH
NH CCH
O
CH2 OH CH2 CH2 SCH3
O
NHCCHH2 N
(CH2 )4 NH2
CH C OH
O
(CH2 )3 NHCNH2
NH
pH = 7
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
(–)
(–)
(N-terminus) (C-terminus)
(+)
(+)
(+)
O
CH C NH CCH
O
NH
CH2 COOH
NH CCH
O
CH2 OH CH2 CH2 SCH3
O
NHCCHH2 N
(CH2 )4 NH2
CH C OH
O
(CH2 )3 NHCNH2
NH
pH = 3
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
(–)
(–)
(N-terminus) (C-terminus)
(+)
(+)
(+)
O
CH C NH CCH
O
NH
CH2 COOH
NH CCH
O
CH2 OH CH2 CH2 SCH3
O
NHCCHH2 N
(CH2 )4 NH2
CH C OH
O
(CH2 )3 NHCNH2
NH
pH = 3
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
(–)
(–)
(N-terminus) (C-terminus)
(+)
(+)
(+)
O
CH C NH CCH
O
NH
CH2 COOH
NH CCH
O
CH2 OH CH2 CH2 SCH3
O
NHCCHH2 N
(CH2 )4 NH2
CH C OH
O
(CH2 )3 NHCNH2
NH
pH = 11
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
(–)
(–)
(N-terminus) (C-terminus)
O
CH C NH CCH
O
NH
CH2 COOH
NH CCH
O
CH2 OH CH2 CH2 SCH3
O
NHCCHH2 N
(CH2 )4 NH2
CH C OH
O
(CH2 )3 NHCNH2
NH
pH = 11
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
(–)
(–)
(N-terminus) (C-terminus)
(5!) = 120 combinations
(20!) = 2.4 1018 eicosapeptides
(205) = 3.2 106 possible pentapeptides
++++H+ or OH-
Arg Asp Lys Met Ser H2OLys – Ser – Met – Asp – Arg
(5!) = 120 combinations
(20!) = 2.4 1018 eicosapeptides
(205) = 3.2 106 possible pentapeptides
++++H+ or OH-
Arg Asp Lys Met Ser H2OLys – Ser – Met – Asp – Arg
(5!) = 120 combinations
(20!) = 2.4 1018 eicosapeptides
(205) = 3.2 106 possible pentapeptides
++++H+ or OH-
Arg Asp Lys Met Ser H2OLys – Ser – Met – Asp – Arg
(5!) = 120 combinations
(20!) = 2.4 1018 eicosapeptides
(205) = 3.2 106 possible pentapeptides
++++H+ or OH-
Arg Asp Lys Met Ser H2OLys – Ser – Met – Asp – Arg
(5!) = 120 combinations
(20!) = 2.4 1018 eicosapeptides
(205) = 3.2 106 possible pentapeptides
++++H+ or OH-
Arg Asp Lys Met Ser H2OLys – Ser – Met – Asp – Arg
(5!) = 120 combinations
(20!) = 2.4 1018 eicosapeptides
(205) = 3.2 106 possible pentapeptides
++++H+ or OH-
Arg Asp Lys Met Ser H2OLys – Ser – Met – Asp – Arg
oxytocin
vasopressin
Cys
Tyr
Phe Gln
Asn
Cys
SS
H2N
O
NH2CGlyArgPro
Cys
Tyr
Ile Gln
Asn
Cys
SS
H2N
O
NH2CGlyLeuPro
CH C NH CCH OH
O O
CH2
OO
HH
NHCCHNHCCHNH
O
HO
NH2
C
Tyr–Gly–Gly–Phe–MetMethionine enkephalin
CH2 CHCH3
CH3
Morphine
O
N
HO OH
CH3
H
H
Tyr–Gly–Gly–Phe–LeuLeucine enkephalin
Enkephalins
SS
Gly–Ile–Val–Glu–Gln–Cys–Cys–Thr–Ser–Ile–Cys–Ser–Leu–Tyr–Gln–Leu–Glu–Asn–Tyr–Cys–Asn
Phe–Val–Asn–Gln–His–Leu–Cys–Gly–Ser–His–Leu–Val–Glu–Ala–Leu–Tyr–Leu–Val–Cys–Gly–Glu–Arg–Gly–Phe–Phe–Tyr–Thr–Pro–Lys–Thr
S5 10 15 3020 25
5 10 15 20
SS
S
Insulin
Structure of Proteins
"
N CH C
H R
N
O
H
CH
R'
C
O O
R"H
CCHN
" R
O
C
R"
CH
H
O
N
R"H
CCHN N CH C
H
O
"
N CH C
H R
N
O
H
CH
R'
C
O O
R"H
CCHN
" R
O
C
R"
CH
H
O
N
R"H
CCHN N CH C
H
O
"
N CH C
H R
N
O
H
CH
R'
C
O O
R"H
CCHN
" R
O
C
R"
CH
H
O
N
R"H
CCHN N CH C
H
O
"
N CH C
H R
N
O
H
CH
R'
C
O O
R"H
CCHN
" R
O
C
R"
CH
H
O
N
R"H
CCHN N CH C
H
O
Secondary Structure: The -Helix
-Pleated Sheet
Random Coil
-helix
-helix-pleated sheet
-pleated sheet
Protein Tertiary Structure
-helix
-helix-pleated sheet
-pleated sheet
salt bridge
NH3
+
-helix
-helix-pleated sheet
-pleated sheet
C-O
O
hydrogenbond
CH2 O
H
CH2O
H
salt bridge
NH3
+
-helix
-helix-pleated sheet
-pleated sheet
C-O
O
hydrogenbond
CH2 O
H
CH2O
H
NH
H
C
OH
O
hydrogenbond
salt bridge
NH3
+
-helix
-helix-pleated sheet
-pleated sheet
C-O
O
hydrogenbond
CH2 O
H
CH2O
H
NH
H
C
OH
O
hydrogenbond
salt bridge
NH3
+
CH2
HO
hydrophilicinteraction
to water
CH2
C
NH2
O
CH2
HO
-helix
-helix-pleated sheet
-pleated sheet
C-O
O
CH2
CH2
hydrophobicinteraction
hydrogenbond
CH2 O
H
CH2O
H
NH
H
C
OH
O
hydrogenbond
salt bridge
NH3
+
CH2
HO
hydrophilicinteraction
to water
CH2
C
NH2
O
CH2
HO
-helix
-helix-pleated sheet
-pleated sheet
C-O
O
CH
CH3 CH3
CH3
CH2
CH2
hydrophobicinteraction
hydrogenbond
CH2 O
H
CH2O
H
NH
H
C
OH
O
hydrogenbond
salt bridge
NH3
+
CH2
HO
hydrophilicinteraction
to water
CH2
C
NH2
O
CH2
HO
-helix
-helix-pleated sheet
-pleated sheet
C-O
O
CH
CH3 CH3
CH3
CH2
CH2
hydrophobicinteraction
S
S
S
Sdisulfide
bond
hydrogenbond
CH2 O
H
CH2O
H
NH
H
C
OH
O
hydrogenbond
salt bridge
NH3
+
CH2
HO
hydrophilicinteraction
to water
CH2
C
NH2
O
CH2
HO
-helix
-helix-pleated sheet
-pleated sheet
C-O
O
Protein Quaternary Structure
C3032H4816N735O780S8Fe4 (MW 64,450)
Hemoglobin
Sickle-Cell Anemia
Sequence Varies: Ask 23andMe
Proteins
Denaturation
Denaturation… also knownas “Cooking”
Misfolding Diseases
Mutation Impairs Proper Folding
Cystic Fibrosis
Sickle CellAnemia
Contagious Misfolding: Prions