Transcript Epjj Lecture 3x

Lecture 3-Amino Acid & Protein
Ahmad Razali Ishak
Department of Environmental Health
Faculty of Health Sciences
UiTM Puncak Alam
1
Function of Protein
 Catalysts- enzymes for metabolic pathway
 Storage and transport- myoglobin and
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hemoglobin
Structural- actin, myosin
Decoding information- translation and gene
expression
Hormones and hormone receptors
Specialized functions-antibodies
Amino Acids- Primary structure of
protein
 Amino acid: a compound that contains
both an amino group and a carboxyl
group
  -Amino acid has an amino group
attached to the carbon adjacent to
the carboxyl group
 -carbon also bound to side chain
group, R
 R gives identity to amino acid
Cont..
 The  - carbon is chiral/asymmetric (4 different
groups are attached to the carbon: exception is
glycine )- mirror image, non super imposable
 AA exist as stereoisomer (same molecular
formula, but differ in arrangement of groups) –
designated D (right) or L (Left)
• Vast majority of  -amino acids have the L-
configuration at the  -carbon (Proline is usually
D)
 -amino group orientation determines L or D
 NH3+ on left = L
 NH3+ on right = D
 Carboxylate group at top- point away side chain
at the bottom
AA structure and properties
 AA are grouped based upon the properties and structures of
side chains
 Aliphatic (R groups consist of carbons and hydrogens)Glycine, Alanine, Valine, Leucine, Isoleucine, Proline
Sulfur containing R group- methionine,
cysteine
Aromatic (R group have phenyl ring)Phenylalanine, tyrosine
Polar R group - Ser, Thr, Tyr, Cys, Glu
Non Polar R group - Ala, Val, Leu, Ile, Pro.
Phe, Trp, Met.
Cont..
 Basic R group- Histidine, lysine, arginine
 Acidic R group - Glutamate, Aspartate
 Side chain with alcohols – Serine, threonine
Ionization of Simple Amino Acids
 Amino acids are more complicated than simple weak acids
since amino acids have at least 2 ionizing groups.
 Glycine (abbrevation is Gly), for example, has both a
carboxylic acid and an amino group that can ionize:
If we dissolve the free base of Gly in pure water (ie neutral pH),
it will ionize.
The equilibrium is far to the right so most of the Gly is in the
charged form called the Zwitterion and Gly is still neutral
because the + charge is neutralized by the - charge.
Gly is always in the Zwitterion form at neutral pH.
Ionization of Amino Acids
• Remember, amino acids without charged groups on side
chain exist in neutral solution as zwitterions with no net
charge
 If one aa being titrated from acidic condition, you will get
this titration curve
 E.g. Titration curve for glycine
 At given pH, amino acid have different net charge
 The isoelectric point (pI) is the pH at which the amino
acid has no net charge = zwitterion
 If pH > pI, amino acid would be –ve charged
 If pH < pI, amino acid would be positively charged
Isoelectric pH
 Isoelectric pH, pI: the pH at which the majority of molecules of a compound
in solution have no net charge
 the pI for glycine, for example, falls midway between the pKa values for the
carboxyl and amino groups
pI = 1 ( p Ka -COOH + p Ka -N H3 + )
2
= 1 (2.35 + 9.78) = 6.06
2
 Isoelectric pH values for the 20 protein-derived amino acids are given in Table
3.2
Protein Structure
Four Levels of Protein Structure:
1. Primary Structure- Polypeptide backbone- Linear sequence
of amino acid
2. Secondary Structure- regular patterns formed by primary
structure folding-Local Hydrogen bonds along the backbone
3. Tertiary structure- Completely folded polypeptide with one
or more domains. Long distance bonding involving the AA
side chains
4. Quaternary structure- Association of multiple polypeptides.
Protein interactions leading to formation of dimers,
tetramers, etc.
Protein Covalent Structure (Protein Primary
Structure)
I. Peptide Bonds, Peptides and Proteins
 Proteins are sometimes called Polypeptides, since they contain
many Peptide Bonds
The peptide bond is an amide bond
Water is lost in forming an amide bond.
Comparison of an amino acid, a dipeptide
and a tripeptide
Peptides = Mini-Proteins
A pentapeptide -- GlyAlaSerPheGln
1st amino acid is always written on the left and called the Amino
terminal, since it is always the only amino acid of the peptide with a
free alpha-amino group. Last amino acid is always written on the right
and called the Carboxyl terminus, since it is always the only amino
acid of the peptide with a free alpha-carboxylic acid group.
SECONDARY STRUCTURE OF PROTEINS
 In 1950's, Linus Pauling named the first structures he found by X-ray
diffraction, the Alpha Helix and the second structure he found was called
Beta Sheet
 The 2 COMMON Types of Protein Secondary Structure:
a.
Alpha-helix
b. Beta-sheet
-Helix
 Coil of the helix is clockwise or right-handed
 There are 3.6 amino acids per turn
 Repeat distance is 5.4Å
 Each peptide bond is s-trans and planar
 C=O of each peptide bond is hydrogen bonded to the N-H
of the fourth amino acid away
 C=O----H-N hydrogen bonds are parallel to helical axis
 All R groups point outward from helix
-Helix (Cont’d)
-Pleated Sheet
 Polypeptide chains lie adjacent to one another; may be
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parallel or antiparallel
R groups alternate, first above and then below plane
Each peptide bond is s-trans and planar
C=O and N-H groups of each peptide bond are
perpendicular to axis of the sheet
C=O---H-N hydrogen bonds are between adjacent sheets
and perpendicular to the direction of the sheet
-Pleated Sheet (Cont’d)
-Pleated Sheet (Cont’d)
-bulge- a common nonrepetive irregular 2˚ motif in
anti-parallel structure
Myoglobin
 A single polypeptide chain of 153 amino acids
 A single heme group in a hydrophobic pocket
 8 regions of -helix; no regions of -sheet
Quaternary Structure
 Quaternary (4°) structure: the association of
polypepetide monomers into multisubunit proteins
 dimers
 trimers
 tetramers
 Noncovalent interactions
 electrostatics, hydrogen bonds, hydrophobic
Hemoglobin (Hb)
 A tetramer of two -chains (141 amino acids each) and two
-chains (153 amino acids each); 22
Homework
 Describe the difference between alpha-helix and beta-
sheet protein structures.
 Describe the metabolic disorder of proteinphenylketonuria
 Please upload the answer in the i-discuss before next seminar