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Lecture 11

Biochemistry 2280A Lecture Notes - Lecture 11: Steric Effects, Coil Spring, Carboxylic Acid


Department
Biochemistry
Course Code
BIOCHEM 2280A
Professor
Eric Ball
Lecture
11

Page:
of 3
Biochem Notes
Proteins are the largest and most varied class of biological molecules
Many have intricate three-dimensional folding patterns that result in a compact form, but
others do not fold up at all
Still others fold into elongated shapes that give rise to fibrous proteins
The function of proteins depends on their structure
To make a protein, amino acids are connected together by a type of amide bond called
a "peptide bond"
This bond is formed between the alpha amino group of one amino acid and the carboxyl
group of another in a condensation reaction
Multiple amino acids result in a polypeptide, with shorter (< 50 amino acid) ones often
referred to as "peptides"
Because water is lost in the course of creating the peptide bond, individual amino acids
are referred to as "amino acid residues" once they are incorporated
Another property of peptides is polarity: the two ends are different One end has a
free amino group (called the "N-terminus") and the other has a free carboxyl group ("C-
terminus")
polypeptides are elongated by the addition of amino acids to the C-terminal end of the
growing chain
peptides are written N-terminal first; therefore, Gly-Ser is not the same as Ser-Gly or GS
is not the same as SG the connection gives rise to a repeating pattern of "NCC-NCC-
NCC..." atoms along the length of the molecule
If stretched out, the side chains of the individual residues project outwards from this
backbone
The peptide bond is written as a single bond, but it actually has some characteristics of
a double bond because of the resonance between the C-O and C-N bonds six atoms
involved are coplanar, and that there is not free rotation around the CN axis This
constrains the flexibility of the chain and prevents some folding patterns
Primary structure is simply the sequence of residues making up the protein Thus
primary structure involves only the covalent bonds linking residues together
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Secondary structure describes the local folding pattern of the polypeptide backbone and
is stabilized by hydrogen bonds between N-H and C=O groups by far the most
common are the orderly repeating forms known as the α-helix and the β-sheet
An α-helix, as the name implies, is a helical arrangement of a single polypeptide chain,
like a coil spring
The backbone carbonyl and N-H groups are oriented parallel to the axis Each
carbonyl is linked by a hydrogen bond to the N-H of a residue located 4 residues further
on in the sequence within the same chain
All C=O and N-H groups are involved in hydrogen bonds, making a fairly rigid cylinder
3.6 residues per turn, 0.54 nm per turn
In a β-sheet, the polypeptide chain folds back on itself so that polypeptide strands lie
side by side, and are held together by hydrogen bonds
the polypeptide backbone N-H and C=O groups form hydrogen bonds to stabilize the
structure, but unlike the α-helix, these bonds are formed between neighboring
polypeptide (β) strands
the primary structure folds back on itself in either a parallel or antiparallel arrangement,
producing a parallel or an antiparallel β-sheet In this arrangement, side chains
project alternately upward and downward from the sheet
A single polypeptide chain may have different regions that take on different secondary
structures many proteins have a mixture of α-helices, β- sheets, and other types of
folding patterns to form various overall shapes
Several factors come into play: steric hindrance between nearby large side chains,
charge repulsion between nearby similarly-charged side chains, and the presence of
proline and glycine Proline contains a ring that constrains bond angles so that it will
not fit exactly into an α-helix or β-sheet
there is no H on one peptide bond when proline is present, so a hydrogen bond cannot
form
Glycine, with the smallest possible side chain, imparts a great deal of flexibility into the
polypeptide backbone, which can disrupt regular secondary structures such as α-helices
and β-sheets
Tertiary structure describes how regions of secondary structure, including α-helices, β-
sheets, and any other loops and folds, fold together to form the 3D arrangement of a
single polypeptide chain
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Whereas secondary structure is stabilized by H-bonding, all four “weak” forces
contribute to tertiary structure
Polypeptide chains generally contain both hydrophobic and hydrophilic residues
Other forces that contribute to tertiary structure are ionic bonds between side chains,
hydrogen bonds, and van der Waals forces These bonds are far weaker than
covalent bonds, and it takes multiple interactions to stabilize a structure
There is one covalent bond that is also involved in tertiary structure, and that is the
disulfide bond that can form between cysteine residues. This bond is important only in
non-cytoplasmic proteins since there are enzyme systems present in the cytoplasm to
remove disulfide bonds
A domain is an independently-folded part of a protein that folds into a stable structure
A protein may have many domains, or consist only of a single domain Domains are
often separated by a loosely folded region and may create clefts between them
Domains are often not only structural units but functional units as well
Some proteins are composed of more than one polypeptide chain In such proteins,
quaternary structure refers to the number and arrangement of the individual polypeptide
chains Each polypeptide is referred to as a subunit of the protein
The same forces and bonds that create tertiary structure also hold subunits together in
a stable complex to form the complete protein
In some proteins, intertwined α-helices hold subunits together; these are called coiled-
coils
A folded, biologically-active protein is considered to be in its “native” state, which is
generally thought to be the conformation with least free energy
Proteins can be unfolded or “denatured” by treatment with solvents that disrupt weak
bonds
Thus organic solvents that disrupt hydrophobic interactions, high concentrations of urea
or guanidine that interfere with H-bonding, extreme pH or even high temperatures, will
all cause proteins to unfold
Denatured proteins have a random, flexible conformation and usually lack biological
activity
If the denaturing condition is removed, some proteins will re-fold and regain activity
This process is called “renaturation.”
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