Transcript Protein Chemistry

Proteins: Three-dimensional structure
Background on protein composition:
Two general classes of proteins

- long rod-shaped, insoluble proteins. These proteins
are strong (high tensile strength). Examples: keratin, hair,
collagen, skin nails etc…

- compact spherical shaped proteins usually watersoluble. Most hydrophobic amino acids found in the interior away
from the water. Nearly all enzymes are globular… an example is
hemoglobin
Proteins: Three-dimensional structure
Background on protein composition:
Two general classes of proteins
 Fibrous - long rod-shaped, insoluble proteins. These proteins are
strong (high tensile strength). Examples: keratin, hair, collagen,
skin nails etc…

- compact spherical shaped proteins usually watersoluble. Most hydrophobic amino acids found in the interior away
from the water. Nearly all enzymes are globular… an example is
hemoglobin
Proteins: Three-dimensional structure
Background on protein composition:
Two general classes of proteins
 Fibrous - long rod-shaped, insoluble proteins. These proteins are
strong (high tensile strength). Examples: keratin, hair, collagen,
skin nails etc…
 Globular - compact spherical shaped proteins usually watersoluble. Most hydrophobic amino acids found in the interior away
from the water. Nearly all enzymes are globular… an example is
hemoglobin
Proteins: Three-dimensional structure
Background on protein composition:
Two general classes of proteins
 Fibrous - long rod-shaped, insoluble proteins. These proteins are
strong (high tensile strength). Examples: keratin, hair, collagen,
skin nails etc…
 Globular - compact spherical shaped proteins usually watersoluble. Most hydrophobic amino acids found in the interior away
from the water. Nearly all enzymes are globular… an example is
hemoglobin
Proteins can be simple - no added groups or modifications, just amino
acids
Or proteins can be conjugated. Additional groups covalently bound to
the amino acids. The naked protein is called the apoprotein and the
added group is the prosthetic group. Together the protein and
prosthetic group is called the holoprotein. Ex. hemoglobin
Four levels of protein structure
Primary structure: amino acid only. The actual amino acid sequence is
specified by the DNA sequence. The primary structure is used to
determine genetic relationships with other proteins - AKA homology.
Amino acids that are not changed are considered invariant or
conserved.
Primary
sequence is also
used to
determine
important
regions and
functions of
proteins domains.
Four levels of protein structure
Secondary structure: This level is only concerned with the local or close
in structures on the protein - peptide backbone. The side chains are
not considered here, even though they have an affect on the
secondary structure.
Two common
secondary
structures - alpha
helix and beta
pleated sheet
Non- regular
repeating structure
is called a random
coil.
- no specific
repeatable pattern
Four levels of protein structure
Tertiary structure - the overall three-dimensional shape
that a protein assumes. This includes all of the secondary
structures and the side groups as well as any prosthetic
groups. This level is also where one looks for native vs.
denatured state. The hydrophobic effect, salt bridges
And other
molecular
forces are
responsible
for
maintaining
the tertiary
structure
Four levels of protein structure
Quaternary structure: The overall interactions of more
than one peptide chain. Called subunits.
Each of the sub
units can be
different or
identical
subunits,
hetero or
homo – x mers
(ex.
Heterodimer is
a protein
composed of
two different
subunits).
Secondary structure - details
To look at the secondary structure and understand why helices and
sheets are formed we need to first look at the nature of the
peptide backbone.
- In organic chemistry the bond formed between a COOH and NH3+
groups is called the amide. This is similar but different from the
peptide bond.
- The peptide bond if
formed between the
alpha carbon carbonic
acid of one protein and
the amine of another
alpha carbon. The
difference is in the
increased double bond
nature of the bond.
There is lots of
resonance and
therefore no rotation
Secondary structure - details
-
A peptide bond can be thought of as a double bond with four atoms in a
plane.
-
The bonds on either side are freely rotatable
-
The bonds within the plane are fixed.
- The amino acid side groups are usually in the trans conformation. The
exception is the proline amino acid.
- Usually in the cis
conformation- due to the nature
of the side group - amine bond.
Secondary structure - details
The conformation of the backbone is described as Torsion angles or
rotational angles
Occur around the Ca-N [phi] and the Ca-C [psi]
By convention these angles are both set as 180 when in the fully
extended conformation
When viewed form the Ca they are said to increase clockwise
Rotational angles - the two bonds which rotate around the peptide
bond are called the phi and psi (y and f). Called torsional angles
-Due to the crowded environment of a
peptide bond, these torsion angles exists in
the lowest energy state conformation.
That means that the bonds rotate without
breaking the covalent bonds, usually by
rotation.
Ramachandran Diagrams
Phi and Psi angles can be calculated!
A Ramachandran plot shows the
values of the torsional angles and
allows prediction of the
conformation
Blue area – shows sterically allowed
Phi and Psi conformations
Green area – sterically forbidden
conformations – would bring
atoms closer than corresponding
van der Waals distance
(distance of closest contact
between non-bound atoms)
Ramachandran Diagrams
Phi and Psi angles can be calculated!
The angle will depend on the two amino
acids. The steric hindrance
between the functional groups
determine the angle of stability.
There are only limited means of
conformation the sheets and
helices.
Right-handed alpha helix
Left-handed alpha helix
Parallel beta sheet
Anti-parallel beta sheet
Collagen helix
And there are always exceptions!
Proline –Cyclic side chain limits the range of
rotation
It is the most conformationally restricted
amino acid residue
Glycine- The only amino acid without a beta
carbon atom is the smallest of the amino
acids
Has almost unlimited rotational freedom and
can fit into almost any conformation