amino acids & chemical evolution of proteins
TRANSCRIPT
Introduction
• Amino Acids of Proteins
a. General Properties
b. Peptide Bonds
c. Classification & Characterization
d. Acid – Base Properties
e. A Few Words on Nomenclature
Introduction, Cont.
• Optical Activity
a. An Operational Classification
b. The Fisher Convention
c. The Cahn – Ingold – Prelog System
d. Chirality and Biochemistry
Introduction, Cont.
• Nonstandard Amino Acids
a. Amino Acid Derivatives in Proteins
b. Specialized Roles of Amino Acids
Introduction, Cont.
• Chemical Evolution
a. Sickle Cell Anemia: The Influence of
Natural Selection
b. Species Variation in Homologous
Proteins: The Effect of Neutral Drift
c. Evolution Through Gene Duplication
Amino Acids of Proteins General Properties
• pK Values of the 20 Standard
- pK1 refer to the α – Carboxylic Acid
- pK2 refer to the α – Amino Groups
- pKR refer to the Side Groups with Acid-Base
Properties
What is pK ?!
Amino Acids of Proteins General Properties, Cont.
• In chemistry and Biochemistry, a
Dissociation Constant or an Ionization
Constant is a Specific Type of Equilibrium
Constant Used for Reversible Reactions or
Processes
The pK Value is Defined as:
pK = - log Kd
Amino Acids of Proteins General Properties, Cont.
• α – Carboxylic Acid Groups lie in small
range 2.2
• Above pH 3.5 These Groups are almost
Entirely in Their Carboxylate Forms
• α – Amino Groups All Have pK Values
Near 9.4
• Below pH 8.0 These Groups are almost
Entirely in Their Ammonium Ion Forms
Amino Acids of Proteins General Properties, Cont
In the physiological pH Range, Both
the Carboxylic Acid and the Amino
Groups of α – Amino Acids are
Completely Ionized
Amino Acids of Proteins General Properties, Cont
• Substances with this Property are Said to
be “Amphoteric” or “Ampholytes”
What Do we Mean By Amphoteric
Substances?!
Amino Acids of Proteins General Properties, Cont
• Amphoteric Substances are any Substance
reacting as acid and base: able to react
chemically as either an acid or a base
• The Zwitterionic Character of the α – Amino
Acids Has Been Established by Several
Methods
- Spectroscopic Measurements
- X-Ray Crystal Structure Determinations
Amino Acids of Proteins General Properties, Cont
• The Physical Properties of Amino Acids are Characteristic of Ionic Compounds
• Most α – Amino Acids Have Melting Points Nearby 300˚C
• Nonionic Amino Acids Derivatives Usually Melt Around 100˚C
• More Soluble in Polar Solvents
• Most α – Amino Acids are Very Soluble in Water
Amino Acids of Proteins
a. General Properties
b. Peptide Bonds
c. Classification & Characterization
d. Acid – Base Properties
e. A Few Words on Nomenclature
Amino Acids of Proteins
Peptide Bonds
• α – Amino Acids Polymerize Through the
Elimination of Water Molecule
Amino Acids of Proteins
Peptide Bonds, Cont
• The Resulting CO – NH Linkage Is Known
as a Peptide Bond
Amino Acids of Proteins
Peptide Bonds, Cont
• 2 A.A. = Dipeptide
• 3 A.A. = Tripeptide
• 3 < A.A. < 10 = Oligopeptide
• A.A. > 10 = Polypeptide
Proteins are Molecule that Consist of One or
More Polypeptide Chains
Amino Acids of Proteins
Peptide Bonds, Cont
• Polypeptides Range in Length from ~ 40 to
Over 4000 A.A. Residue
• The Average Mass of an A.A. is ~ 110 D
• Therefore the molecular Masses of
Polypeptides Range From ~ 4 to over 440
KD
• Polypeptides are Linear Polymers
Amino Acids of Proteins
Peptide Bonds, Cont
• Huge Number of Different Protein
Molecules Can Exist
• For Example: A Small Protein Molecule
Consists of a Single Polypeptide Chain of
100 Residue of A.A. Can Form 20100
Possible Unique Polypeptide Chain of This
Length
Amino Acids of Proteins
Peptide Bonds, Cont
The Various organisms on Earth
Collectively Synthesize an Enormous
Number of Different Protein
Molecules whose Great Range of
Physicochemical Characteristics Stem
Largely from the Varied Properties of
the 20 “Standard” Amino Acids
Amino Acids of Proteins
a. General Properties
b. Peptide Bonds
c. Classification & Characterization
d. Acid – Base Properties
e. A Few Words on Nomenclature
Amino Acids of Proteins
Classification & Characterization
• The Polarity of A.A’s. Side Chain (R Groups)
is the Most Useful Way to Classify the 20
Standard A.A.
• Proteins Fold in Response to Tendency
to Remove Their Hydrophobic Side Chain
from Contact with Water and to Solvate
Hydrophilic Side Chain
• According to that Classification Scheme,
there are Three Major Types of A.A.
Amino Acids of Proteins
Classification & Characterization, Cont
1- Nonpolar A.A. Side Chains
• Glycine: Was the First A.A. to be Identified
& has the Smallest Possible Side Chain, an
H Atom.
Amino Acids of Proteins
Classification & Characterization, Cont
• Alanine, Valine, Leucine & Isoleucine:
Have Aliphatic Hydrocarbon Side Chains
Amino Acids of Proteins
Classification & Characterization, Cont
• Methionine: Has a a Thiol Ether Side
Chain
• Proline: A Cyclic Secondary A.A. has
Conformational Constraints Imposed by
the Cyclic nature of it’s Pyrrolidine Side
Group
Amino Acids of Proteins
Classification & Characterization, Cont
• Phenylalanine: With it’s Phenyl Moiety,
Contain Aromatic Side Group Which is
Characterized as Nonpolar Group
Amino Acids of Proteins
Classification & Characterization, Cont
• Tryptophan: With it’s Indole Group,
Contain Aromatic Side Group Which is
Characterized as Nonpolar Group
Amino Acids of Proteins
Classification & Characterization, Cont
2- Uncharged Polar A.A. Side Chains
• Serine & Threonine: Bear Hydroxylic R
Group of Different Sizes
Amino Acids of Proteins
Classification & Characterization, Cont
• Asparagine & Glutamine: Have Amide-
Bearing Side Chains of Different Sizes
Amino Acids of Proteins
Classification & Characterization, Cont
• Tyrosine: Has a Phenolic Group, which,
together with Aromatic Groups of
Phenylalanine & Tryptophan Accounts for
Most of the UV Absorbance and
Fluorescence Exhibited by Proteins
Amino Acids of Proteins
Classification & Characterization, Cont
• Cysteine: Has a Thiol Group Which is
Make Disulfide Bond with other Cysteine
Molecule, it means that it can Join
Separate Polypeptide Chains or Cross-Link
Two Cysteine in the Same Chain
Amino Acids of Proteins
Classification & Characterization, Cont
3- Charged (Positively) Polar A.A. Side Chains
• Lysine: Has a Butylammonium Side Chain
• Arginine: Has Guanidino Group
Amino Acids of Proteins
Classification & Characterization, Cont
• Histidine: Which Carry Imidazolium Moiety
• Only Histidine with pkR
= 6.0 Ionizes within the Physiological pH
• As a Consequence, Histidine Side Chain often Participate in the Catalytic Reaction of Enzyme
Amino Acids of Proteins
Classification & Characterization, Cont
3- Charged (Negatively ) Polar A.A. Side
Chains
• Aspartic Acid & Glutamic Acid: Are
Negatively Charged above pH = 3.0
Amino Acids of Proteins
a. General Properties
b. Peptide Bonds
c. Classification & Characterization
d. Acid – Base Properties
e. A Few Words on Nomenclature
Amino Acids of Proteins
a. General Properties
b. Peptide Bonds
c. Classification & Characterization
d. Acid – Base Properties
e. A Few Words on Nomenclature
Amino Acids of Proteins
A Few Words on Nomenclature
• The Three Letter Abbreviation
• Widely Used Throughout Biochemical Literature
• The One Letter Symbol
• Often Used when Comparing the A.A. Sequences of Several Similar Proteins
• A.A. in Polypeptides are Named by Dropping the Suffix -ine and Replacing it by -yl
• For example: Alanine Alanyl
Amino Acids of Proteins
a. General Properties
b. Peptide Bonds
c. Classification & Characterization
d. Acid – Base Properties
e. A Few Words on Nomenclature
Optical Activity
a. An Operational Classification
b. The Fisher Convention
c. The Cahn – Ingold – Prelog System
d. Chirality and Biochemistry
Optical Activity
• All A.A. - Except (Gly) - are Optically Active
• Optically Active Molecules Have an
Asymmetry Such that they are not
Superimposable on their mirror Image
• The Central Atom is Known as Chiral Center
• Molecules that are Nonsupeimposable Mirror
Image are Known as Enantiomers
Optical Activity
An Operational Classification
• Molecules are Classified as Dextrorotary (Greek: Dextro, right) or Levorotary (Greek: Levo, left)
• This Can be Determined by an Instrument Known as a Polarimeter
• The Quantitative measure of the Optical Activity of the Molecule is Known as it’s Specific Rotation
Observed Rotation
[α]25
=
D
Optical Path Length (dm) X Concentartion (gf. Cm-3
)
Optical Activity
a. An Operational Classification
b. The Fisher Convention
c. The Cahn – Ingold – Prelog System
d. Chirality and Biochemistry
Optical Activity
The Fisher Convention
• The Configuration of the Groups About an
Asymmetric Center is related to that of
Glyceraldehyde
Optical Activity
The Fisher Convention
• Fischer Projections are Abbreviated Structural Forms that Allow One to Convey Valuable Stereochemical Information to a Chemist without them Having to Draw a 3D Structural Representation of a Molecule
• Horizontal Lines Represent Bonds Coming Out of the Plane of the Paper and Vertical Lines Represent Bonds Going Behind the Plane of the Paper.
Optical Activity
a. An Operational Classification
b. The Fisher Convention
c. The Cahn – Ingold – Prelog System
d. Chirality and Biochemistry
Optical Activity
The Cahn – Ingold – Prelog System
• Fischer Scheme is Awkward for Molecules with More than One Asymmetric Center
• The Four Groups Surrounding a Chiral Center are Ranked According to a Specific Scheme:
Atoms of Higher Atomic Number Bonded
to a Chiral Center are Ranked Above
those of Lower Atomic Number
Optical Activity
The Cahn – Ingold – Prelog System
• For Example: the Oxygen of OH Group
Takes Precedence Over the Carbon Atom
of a CH3 Group that is Bonded to the Same
Chiral Center
• The Order of Priority of Some Common
Functional Groups is:
SH > OH > NH2 > COOH > CHO > CH2OH > C6H5 > CH3 > 2H > 1H
Optical Activity
The Cahn – Ingold – Prelog System
• The Prioritized Groups are Assigned the Letters : W, X, Y, Z
• The Order of Priority Rating is:
W > X > Y > Z
• If the Order of the Groups W X Y is Clockwise, then the Configuration of Asymmetric Center is Designated (S)
• If the Order of the Groups W X Y is Counterclockwise, then the Configuration of Asymmetric Center is Designated (R)
Optical Activity
a. An Operational Classification
b. The Fisher Convention
c. The Cahn – Ingold – Prelog System
d. Chirality and Biochemistry
Optical Activity
Chirality and Biochemistry
• The Biosynthesis of a Substance
Possessing Asymmetric Centers Almost
Invariably Produces a Pure Stereoisomer
• The L Configuration of A.A. is One Example
of this Phenomenon
Optical Activity
a. An Operational Classification
b. The Fisher Convention
c. The Cahn – Ingold – Prelog System
d. Chirality and Biochemistry
Nonstandard Amino Acids
• The 20 Common A.A. are the Only A.A.
that Occur in Biological Systems
• Nonstandard A.A. Residue are Often
Important Constituents of Proteins and
Biologically Active Polypeptides
• Many A.A., However, are not Constituents
of Proteins
Nonstandard Amino Acids
Amino Acid Derivatives in Proteins
• In All Known Cases But One (Section 30-2D-P: 923), However, These Unusual A.A. Result From The Specific Modification of an A.A. Residue After the Polypeptide Chain Has Been Synthesized
• Famous Modified A.A.:
4 - hydroxyproline
5 - hydroxyproline
• Important Structural Constituents of the Fibrous Protein Collagen
Nonstandard Amino Acids. Specialized Roles of Amino Acids
• Nature Tends to Adapt Materials and
Processes that are Already Present to a New
Functions
• Chemical Messenger Between Cells
Neurotransmitters:
Glycine
GABA = Glutamate Decarboxylation Product)
Dopamine = ( Tyrosine Product)
Nonstandard Amino Acids. Specialized Roles of Amino Acids
Mediator of Allergic Reaction:
Histamine (Histidine Decarboxylation Product)
Hormone:
Thyroxin
Important Intermediates in Metabolic Pathways:
Ornithine
Homocysteine
S - Adenosylmethionine