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