Lecture
3: Macromolecules: Their Chemistry and Biology – 9/5/01
Macromolecules:
Giant Polymers
Types
of biological macromolecules: proteins, carbohydrates, lipids, and nucleic
acids. Building blocks: Table 3.1
Some
types of macromolecules contain many different kinds of monomers.
Some
contain the same simple units, repeated many times.
High
Interest:
Structure
Determination -> function
Establish
function through genetic mutants; change structure -> change in function
Structure
Prediction
Rational
Drug Design: vs Irrational Drug Design
Irrational
(previous norm!) – make lots of random compounds, test them using a technique
called High Throughput Screening
Rational
– new model – evaluate shape of active site surface, find compounds that will
have a shape that blocks site
Differences between monomer
units vs polymers: entropy.
Synthesis:
Condensation Reactions
Macromolecules
are made from smaller monomers by removing an OH from one monomer and an H from
another monomer to link them together; water is given off as a result. (See Figure
3.2.) Condensation or dehydration (loss of water) reaction.
Energy
must be added to make or break a polymer; bonding favorable
The
reverse reaction, breaking polymers back into monomers, is a hydrolysis
reaction (hydro means water; lysis, break).
A
hydrolysis reaction is one in which water is added and reacts with the bond
that links the units together.
It takes special proteins, called enzymes, to make
polymers from monomers. Protein synthesis occurs
within the ribosome: the active enzyme here is a ribozyme [strands of RNA
acting as an enzyme}
Most hydrolysis in biological systems is also
performed by enzymes, although a strong acid or base solution can hydrolyze
many types of polymers.
In people, stomach
acid hydrolyzes some of the linkages found in the polymers
we eat.
Proteins: Polymers
of Amino Acids
Drawing
of a condensation rxn: 2 amino acids -> polypeptide. (Fig 3.2:
resonance of single to double bond structure helps stabilize the peptide bond,
CONH
Proteins
called enzymes are particularly
important in biological systems. Enzymes increase the rates of chemical
reactions in cells. This function is known as catalysis.
Enzymes
are highly specific; in general, each enzyme catalyzes only one chemical
reaction.
Proteins
range in size from a few amino acids to thousands.
Some
proteins are composed of a single chain of amino acids, called a polypeptide.
Other
proteins have more than one polypeptide chain. [Quaternary structure!]
Folding
is crucial to the function of a protein. Folding is influenced largely by the
sequence of amino acids. The final
folded structure is the Tertiary structure.
Each different type of protein has a characteristic amino acid composition and order. [Primary structure!]
Proteins are composed
of amino acids
Differences
in amino acids come from the side chains, or the R groups, found attached to
the same carbon as the amino group. (See Table 3.2A-D.)
The 20
common amino acids vary widely in properties
All
but one have four different groups that are attached to the a carbon.
A
hydrogen atom, an amino group, and a carboxyl group are bonded to the a carbon of all the different amino acids.
The
fourth group, the R group, is what makes one type of amino acid different from
another.
Glycine
has H as its R group and is, therefore, the only amino acid that has three
rather than four groups attached to the a carbon.
Carbons with four different
groups attached can exist in different stereoisomeric (handedness) forms. All amino acids do, except for glycine.
Amino
acids can be classified based on the characteristics of their R groups.
Five
of the 20 amino acids form ions in solution depending on pH [charged R groups].
Four
of the 20 have polar side chains [polar R groups].
Eight
have nonpolar R groups [hydrophobic R groups].
Three
amino acids, cysteine, glycine, and proline, have some special properties.
Cysteine
has a terminal sulfhydryl (SH) group which often forms a disulfide (—S—S—)
bridge with another cysteine. (See
Figure 3.3.)
Glycine
has a hydrogen atom as the side chain. This group is small enough to fit into
small spaces and tight corners when the protein folds.
Proline
has a modified amino group that forms a covalent bond with the R group.
Proline's
ring limits rotation of the a carbon’s bond.
Proline
is often found at bends and loops of proteins.
Peptide linkages
covalently bond amino acids together
Proteins
are synthesized by condensation reactions between the amino group of one amino
acid and the carboxyl group of another. This forms a peptide linkage. (See
Figure 3.4.) See Cech’s article, The
Ribosome is a Ribozyme.
Proteins
are also called polypeptides. A dipeptide is two amino acids long; a
tripeptide, three; oligo, a bunch. A polypeptide is multiple amino acids long.
The first
amino acid of a peptide is called the N-terminus amino acid because the amino
group is free, or unbound.
The
last is called the C-terminus amino acid and has a free carboxyl group.
The
C–N peptide linkage forms a partial double bond, which is a single covalent and
polar attraction.
This
bond limits folding and restricts the ability of the adjacent atoms to rotate.
Within
the central axis of the protein, there is an asymmetry of charge favoring a
tendency toward hydrogen bonding. (Oxygen is partially negative and nitrogen is
slightly positive.)
The primary structure
of the protein is its amino acid sequence.
There
are four levels of protein structure: primary, secondary, tertiary, and
quaternary. (See Figure 3.5.)
The
precise sequence of amino acids is called its primary structure.
The
peptide backbone is repeating units of atoms: N—C—C—N—C—C…
In
the figure, the portion on the left is the N terminus; on the right is the C
terminus.
The
protein is synthesized starting from the N terminus and adding to the C
terminus.
Many
proteins have now been sequenced.
The
two conventions for representing the sequence are three-letter and one-letter
systems. (See Table 3.2.)
In the three-letter system,
methionine is Met; in the one-letter system, it is M.
Amazing
numbers of different proteins are possible. N20
The secondary
structure of a protein requires hydrogen bonding
Secondary
structure is the shape regions of the peptide take on as a folded polymer.
This
shape is influenced primarily by the amino acid sequence (the primary
structure).
There
are two common secondary structures.
One
is the a helix, a right-handed coil.
(See Figure 3.5b.)
The
peptide backbone takes on the helical shape due to hydrogen bonds.
The
R groups point away from the peptide backbone.
Large
R groups tend to prevent the creation of this structure.
Insoluble
fibrous structural proteins have a-helical secondary
structures. Examples are the proteins found in hair, feathers, and hooves,
called keratins.
Hair
stretches because only hydrogen bonds, not covalent bonds, are broken when it
is pulled.
Another
common secondary structure is b pleated sheets.
These
form from peptide regions that lie parallel to each other. (See Figure 3.5c.)
Sometimes
the parallel regions are in the same peptide.
Sometimes
the parallel regions are from different peptide strands.
This
sheet-like structure is stabilized by hydrogen bonds between N—H groups on one
chain with the C=O group on the other.
Spider
silk is made of b pleated sheets from separate
peptides. Despite the weakness of the hydrogen bonds, together they tend to be
additive; therefore, substances like spider silk can be remarkably strong.
The tertiary structure
of a protein is formed by bending and folding
Tertiary
structure is the three-dimensional shape of the completed polypeptide. (See
Figure 3.5d.)
Lysozyme:
Fig 3.6: compare with Hen.lysozyme.1PBX.prt
The
primary determinant of the tertiary structure is the interaction between R
groups, which is determined by the protein’s primary structure.
Other
factors are
The
nature and location of secondary structures
The
location of disulfide bridges, which form between cysteine residues
Hydrophobic
side chain aggregation and van der Waals forces, which help stabilize them
The
ionic interactions, the positive and negative charges deep in the protein away
from water
The quaternary
structure of a protein consists of subunits
Some
proteins are composed of subunits, which are separate peptide chains that
associate together to create the functional protein. (See Figure 3.5e.)
This
dimension is called the quaternary structure, and it adds to the 3-D shape of
the finished protein.
Quaternary
structure results from the ways in which multiple polypeptide subunits bind
together and interact.
Hemoglobin
is an example of such a protein; it has four subunits, 2 alpha units and 2 beta
units. (See Figure 3.7.)
Protein shapes are
sensitive to the environment
Changes
in temperature, pH, salt concentrations, and oxidation or reduction conditions
can change the shape of proteins. This process is called denaturation. (See Figure 3.9.)
Often
denaturation is irreversible, like the boiling of egg white.
Some
chemically induced changes are reversed by removal of the chemical condition
that caused them.
A few proteins, like ribonuclease, resist
denaturation; they can be boiled for days and retain activity once cooled.