Proteins

Proteins

 The most important type

of macromolecule.
 Roles:
 Structure: collagen in skin,
keratin in hair, crystallin in
eye. Also slimy substances
like mucus and the
bacterial capsule.
 Enzymes: all metabolic
transformations, building
up, rearranging, and
breaking down of organic
compounds, are done by
enzymes, which are
proteins.
 Other macromolecules
such as carbohydrates
and lipids are created
by enzymes from
smaller molecules.
 Transport: oxygen in the blood is carried by hemoglobin,
everything that goes in or out of a cell (except water and a
few gasses) is carried by proteins.
 Also: nutrition (egg yolk), hormones, defense, movement
 Enzymes are usually roughly globular, while structural
proteins are usually fiber-shaped. Proteins that transport
materials across membranes have a long segment of
hydrophobic amino acids that sits in the hydrophobic
interior of the membrane.
 Close relationship between protein structure and its function

Example of enzyme reaction Hormone receptor Antibody

substrates
enzyme A enzyme

Matching
Digestion
the shape
of A!
to A enzyme

Binding to A
 Amino Acids

 Amino acids are the subunits of proteins.

 20 amino acids coded in DNA.
 The properties of the protein are determined by the R-groups on
the amino acids
 They have a central α-carbon and α-amino and α-carboxyl groups
 Same core structure, but different side group (R)
 The α-C is chiral (except glycine); proteins contain only L-
isoforms.
 Amino acids are ampholytes, pKa of α-COOH is ~2 and of α-NH2
is ~ 9
 At physiological pH most aa occur as zwitterions
Classification

 hydrophobic (found in membranes and protein

interiors): Leucine, isoleucine, valine, methionine,
phenylalanine, tryptophan

 positively charged (basic): lysine, arginine, histidine

 negatively charged (acidic): aspartate, glutamate

 polar but uncharged: serine, threonine, asparagine,

glutamine

 chain bending (imino acid): proline

 disulfide bridge forming: cysteine

 Small: glycine, alanine, serine

 Classification of Amino Acids (Based on R-group)

 Aliphatic: gly (G), ala (A) , val (V), leu (L), ile (I)
 Aromatic: Trp (W), Phe (F), Tyr (Y), His (H),
 Sulphur : Met (M), Cys (C)
 Hydroxyl: Ser (S), Thr (T), Tyr (Y)
 Cyclic: pro (P)
 Carboxyl: asp (D), glu (E)
 Amine: lys (K), arg (R)
 Amide: asn (N), gln (Q)
Another View of Amino Acid Properties
One Letter Amino Acid
Codes
 Properties of the 20 amino
acids that Primary
occur inStructure
peptides- Amino Acids

and proteins are crucial to the

structure and function of
proteins
 Stereochemistry

 Relative hydrophobicity or
polarity
 Hydrogen bonding properties

 Ionization properties

 Other chemical properties

α-Amino Acids, Ionization
 Amino acids in solution at neutral pH exist predominantly
as dipolar ions (also called zwitterions).
 In the dipolar form, the amino group is protonated (-NH3
+) and the carboxyl group is deprotonated (-COO-).
 The ionization state of an amino acid varies with pH.
 In acid solution (e.g., pH 1), the amino group is protonated
(-NH3 +) and the carboxyl group is not dissociated (-
COOH).
 As the pH is raised, the carboxylic acid is the first group to
give up a proton, inasmuch as its pK a is near 2.
 The dipolar form persists until the pH approaches 9, when
the protonated amino group loses a proton.
 α-COOH group: a weak acid
 can DONATE its proton
 pKa ~ 2-3
 α-NH2 group: a weak base
 unshared pair of electrons on the :N
 neutral amino group can ACCEPT a proton.
 pKa ~9-10
 pKas of α-amino and α-carboxyl groups are different for
different amino acids, and also are altered if they're the
terminal groups on chain of AAs, i.e., a peptide or protein.
 Besides the α-carboxyl and α -amino groups, 7 of the 20 AAs
have ionizable side chains.
 Levels of Structure

 A polypeptide is one linear chain of amino acids. Each

gene produces one polypeptide. A protein may contain
one or more polypeptides. Proteins also sometimes
contain small helper molecules (co-factors) such as heme.

 The primary structure (1o) is the sequence of amino acids

in the polypeptide.
 The secondary structure (2o) is local folding patterns,
mostly alpha helix and beta sheet.

 The tertiary structure (3o) is the overall folding pattern of

the entire polypeptide.

 The quaternary structure (4o) is the joining of individual

polypeptides (subunits) into an active protein. Proteins
that are just a single monomeric polypeptide have no
quaternary structure.
 Hierarchical nature of protein structure

Primary structure (Amino acid sequence)

↓
Secondary structure （ α-helix, β-sheet ）
↓
Tertiary structure （ Three-dimensional structure formed by
assembly of secondary structures ）
↓
Quaternary structure （ Structure formed by more than one
polypeptide chains ）
Primary Structure: Amino
Peptide BondAcids Are Linked by Peptide Bonds to
Formation
Form Polypeptide Chains
Polypeptide chains are flexible yet conformationally restricted
 Peptide
 The peptide bond, Bond
the C=O Conformation
bonded to N-H, is a rigid planar
structure, with the O and N atoms in trans.
 Partial double bond character due to resonance structures of
peptide bond (bond length is 1.32 Ao instead of 1.49 Ao
(single) or 1.27 Ao (double)
 Due to steric hindrance, all peptide bonds in proteins are in
trans configuration
 An exception: proline creates a bond in the cis configuration,
because the N is bonded to the alpha carbon through the
side chain.
 The 2 bonds around the α-carbon have freedom of rotation
making proteins flexible to bend and fold
The bonds between the amino group and the alpha carbon atom
and between the alpha carbon atom and the carbony group is
single bond and has freedom of rotation – allows proteins to fold
in many different ways – specified by dihedral angles. The angle
of rotation about the bond between the nitrogen and the alpha
carbon atom is called phi (φ) and the bond between alpha
carbon atom to the carbonyl is called psi (ψ).
The φ and ψ values determine the path of the polypeptide chain.

N
 The values of phi and psi are constrained to certain
values based on steric clashes of the R group. Thus
these values show characteristic patterns as defined by
the Ramachandran plot
 Ramachandran Diagrams

 When the phi and psi angles

from a large number of
proteins are plotted, it is
found that most amino acids
fall into a small part of the
possible bond angles.

 These diagrams give rise to

the notion of two main
secondary structures, the
alpha helix and the beta
sheet.
 There are also left-handed
alpha helices and epsilon
structures, but they are
rarer.

 These structures are held

together by hydrogen bonds
between the atoms of the
peptide bond.
 Ramachandran Plot
Ramachandran Plot

 Shows allowed and disallowed regions

 Gly and Pro are exceptions: Gly has no limitation; Pro is

constrained by the fact its side chain binds back to the
main chain