Molecular Biophysics Lecture 2 Protein Structure II
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Transcript of Molecular Biophysics Lecture 2 Protein Structure II
Molecular BiophysicsLecture 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
Na D Line passed through polarizing filters.
}Operational
definition only cannot predict
absolute configurations
One or many chiral centers
N chiral centers 2N possible stereoisomers and 2N-1 are enantiomericFor N = 2there are 4 possible sterioisomers of which 2 are enatiomersand 2 are diastereomers
Diastereomers are not mirror images and have different chemical properties.
StereoisomersStereoisomers
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
An example of an amino acid with two asymmetric carbons
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
All naturally occurring amino acids that make up proteins are in the L conformation
The CORN method for L isomers: put the hydrogen towards you and read off CO R N clockwise around the C 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
HelicesA repeating spiral, right handed (clockwise twist)
helixpitch = p
Number of repeating units per turn = n
d = p/n = Rise per repeating unit
Fingers of a right - hand.
Several types , 2.27 ribbon, 310 , helicies, orthe most common is the 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 helix.
•Pi helix 4.416 4.4 residues per turn. Not seen!!
Properties of the helix
• 3.6 amino acids per turn• Pitch of 5.4 Å• O(i) to N(i+4) hydrogen bonding• Helix dipole• Negative and angles, • Typically = -60 º and = -50 º
Proline helixLeft 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 () 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 Beta-Sheets
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 beta-bulges) 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 () sheet
• Extended zig-zag
conformation • Axial distance 3.5 Å• 2 residues per repeat• 7 Å pitch