Transcript Lecture 2 Thurs17 Oct

Molecular Biophysics
Lecture 2
Protein Structure II
12824 BCHS 6297
Lecturers held Tuesday and Thursday
10 AM – 12 Noon 402B-HSC
Optical activity - The ability to rotate plane - polarized
light
Asymmetric carbon atom
Chirality - Not superimposable
Mirror image - enantiomers
(+) Dextrorotatory - right - clockwise
(-) Levorotatory - left counterclockwise
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Na D Line passed through polarizing filters.
Operational
definition only
cannot predict
absolute
configurations
Stereoisomers
One or many chiral centers
N chiral centers 2N possible stereoisomers and 2N-1 are
enantiomeric
For N = 2
there are 4 possible sterioisomers
of which 2 are enatiomers
and 2 are diastereomers
Diastereomers are not mirror images and have
different chemical properties.
The Fischer Convention
Absolute configuration about an asymmetric carbon
related to glyceraldehyde
(+) = D-Glyceraldehyde
(-) = L-Glyceraldehyde
An example of an amino acid with
two asymmetric carbons
All naturally occurring amino acids that make up
proteins are in the L conformation
In the Fischer projection all bonds in the horizontal
direction is coming out of the plane if the paper, while
the vertical bonds project behind the plane of the paper
The CORN method for L
isomers: put the hydrogen
towards you and read off
CO R N clockwise
around the Ca This works
for all amino acids.
Cahn - Ingold - Prelog system
Can give absolute configuration nomenclature to multiple
chiral centers.
Priority
Atoms of higher atomic number bonded to a chiral center
are ranked above those of lower atomic number with
lowest priority away from you R highest to lowest =
clockwise, S highest to lowest = counterclockwise
SH>OH>NH2>COOH>CHO>CH2OH>C6H5>CH3>H
Newman Projection
• A projection formula representing the spatial arrangement of
bonds on two adjacent atoms in a molecular entity.
• The structure appears as viewed along the bond between these
two atoms, and the bonds from them to other groups are drawn
as projections in the plane of the paper.
• The bonds from the atom nearer to the observer are drawn so as
to meet at the centre of a circle representing that atom.
• Those from the further atom are drawn as if projecting from
behind the circle.
The major advantage of the CIP or RS system is
that the chiralities of compounds with multiple
asymmetric centers can be unambiguously
described
Prochiral substituents are
distinguishable
Two chemically identical substituents to an
otherwise chiral tetrahedral center are geometrically
distinct.
Planar objects with no rotational symmetry also
have prochariality
Flat trigonal molecules such as aldehydes can be prochiral
With the flat side facing the viewer if the priority is
clockwise it is called the (a) re face (rectus) else it is the
(b) si face (sinistrus).
Protein Geometry
CORN LAW amino acid with L configuration
Greek alphabet
Peptide Torsion Angles
Torsion angles determine flexibility of backbone structure
Side Chain Conformation
Sidechain torsion rotamers
• named chi1, chi2, chi3, etc.
e.g. lysine
chi1 angle is restricted
• Due to steric hindrance between the gamma side chain
atom(s) and the main chain
• The different conformations referred to as gauche(+),
trans and gauche(-)
• gauche(+) most common
Helices
A repeating spiral, right handed (clockwise twist)
helix
pitch = p
Number of repeating units per turn = n
d = p/n =
Rise per repeating unit
Fingers of a right - hand.
Several types a, 2.27 ribbon, 310 ,  helicies, or
the most common is the a helix.
Examples of helices
The Nm nomenclature for helices
N = the number of repeating units per turn
M = the number of atoms that complete the cyclic
system that is enclosed by the hydrogen bond.
The 2.27 Ribbon
•Atom (1) -O- hydrogen bonds to the 7th atom in the
chain with an N = 2.2 (2.2 residues per turn)
3.010 helix
•Atom (1) -O- hydrogen bonds to the 10th residue in
the chain with an N= 3.
•Pitch = 6.0 Å occasionally observed but torsion
angles are slightly forbidden. Seen as a single
turn at the end of an a helix.
•Pi helix 4.416 4.4 residues per turn. Not seen!!
Properties of the a helix
•
•
•
•
•
•
3.6 amino acids per turn
Pitch of 5.4 Å
O(i) to N(i+4) hydrogen bonding
Helix dipole
Negative f and y angles,
Typically f = -60 º and y = -50 º
Proline helix
Left handed helix
3.0 residues per turn
pitch = 9.4 Å
No hydrogen bonding in the backbone but
helix still forms.
Solvent exposure of the carbonyl oxygen is
favored in this confomation
Poly glycine also forms this type of helix
Collagen: high in Gly-Pro residues has this type
of helical structure
Top view along helix axis
Helical bundle
Distortions of alpha-helices
• The packing of buried helices against other
secondary structure elements in the core of
the protein.
• Proline residues induce distortions of around
20 degrees in the direction of the helix axis.
(causes two H-bonds in the helix to be
broken)
• Solvent. Exposed helices are often bent away
from the solvent region. This is because the
exposed C=O groups tend to point towards
solvent to maximize their H-bonding capacity
Helical propensity
beta (b) sheet
• Extended zig-zag
conformation
• Axial distance 3.5 Å
• 2 residues per repeat
• 7 Å pitch
Antiparallel beta sheet
Antiparallel beta sheet side view
Parallel beta sheet
Parallel, Antiparallel and Mixed BetaSheets
Beta sheets are twisted
• Parallel sheets are less twisted than antiparallel and are always buried.
• In contrast, antiparallel sheets can withstand greater distortions (twisting and betabulges) and greater exposure to solvent.
LFA-1 secondary structure
Reverse Turns
Beta-Hairpin turns
• occur between two antiparallel beta-strands
• most common types I' and II'
two-residue turns
beta (b) sheet
• Extended zig-zag
conformation
• Axial distance 3.5 Å
• 2 residues per repeat
• 7 Å pitch