S.Prasanth Kumar, S.Prasanth Kumar, BioinformaticianBioinformatician

Proteins

Secondary Structural Elements with special Secondary Structural Elements with special attention to Ramachandran Plotattention to Ramachandran Plot

S.Prasanth Kumar Dept. of Bioinformatics Applied Botany Centre (ABC) Gujarat University, Ahmedabad, INDIA

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Coined : Linderstrom-Lang and Schnellman 1959

Primary & Secondary Structure

Primary structure refers to the linear sequence of amino acid residues in a polypeptide chain

MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

Secondary structure refers to the arrangements of the primary amino acid sequence into motifs such as alpha helices, beta sheets, and coils (or loops)

Secondary Structure : Example

Tertiary Structure

The tertiary structure is the three-dimensional arrangement formedby packing secondary structure elements into globular domains

Quaternary Structure

Quaternary structure involves the arrangement of several polypeptidechains

Peptide Bond & Phi-Psi Angles

Phi is the angle around the N-Ca bondPsi is the angle around the Ca-C’ bond

In glycine, the R group is a hydrogen and thus amino acid is not chiral

Secondary Structure

Glycine is an exceptional amino acid because it has the flexibility to occur at phi-psi combinations that are not tolerated for other amino acids

For most amino acids the phi and psi angles are constrained to allowable regions in which there is a high propensity for particular secondary structures to form

Linus Pauling and Robert Corey (1951) described the secondary structures : alpha helix and beta pleated sheets from hemoglobin, keratins, etc

Type of Helices

Alpha

3.10*

Pi

Amino acid per turn

3.6

3.0

4.4

Occurrence in structure

97%

3 %

rare

*more tightly packed

Ramachandran Plot

A Ramachandran plot displays the phi and psi angles for essentially all amino acids in a protein (proline and glycine are not displayed)

Why Glycine and Proline are not treated ?

Glycine’s has more flexibility, phi-psi combinations not tolerated

Proline is extremely unlikely to occur in an a helix, and it is often positioned at a turn

You Should Add later information

Secondary-Structure Prediction Programs

Ramachandran Plot

Ramachandran Plot

The distribution of phi and psi angles for a total of 9,156 amino acid residues from 4,413 protein chains, based on crystallographic data

2 areas where the density of points is high(1) Around phi= -60° and psi= -60° corresponds to the a-helix(2) Around phi= -90° and psi= -120° corresponds to the b-structure

Nonpolar, aliphatic R groups

Glycine and Proline

Glycine has a much wider low-energy area because it does not have a Ca atom

Proline has its side chain covalently bound to backbone amine; hence its phi angle is limited to the range of phi = -60° +/- 20°

Glycine is formally nonpolar, its very small side chain makes no real contribution to hydrophobic interactions

Proline has an aliphatic side chain with a distinctive cyclic structure. The secondary amino (imino) group of proline residues isheld in a rigid conformation that reduces the structural flexibility of polypeptide regions containing proline

Ramachandran Map

The highly occupied areas of these plots have a good correspondence with low energy conformation of amino acid residues

Helices

Protein helices are stabilized by hydrogen bonds between the amino and carboxyl groups of the amino acid residue main chains: i, i + 3 (3.10-helix) i, i + 4 (a-helix)i, i + 5 (a-helix)

The average length of the a-helix is about 10–11 residues, which is approximately 17A˚ , or three helical turnsThe main chain angles in the a-helix are approximately phi = psi = -60 ˚

Ala, Glu, Leu, and Met are often foundPro, Gly, Ser, Thr, and Val occur relatively rarely

3.10-helix equal approximately -60 ˚ and -30 ˚

Helices

Proline mainly occurs in the first turn of an a-helix because it can not donatea hydrogen bond in the middle of a helix, and it creates sterical problems in a-helical conformation

In a regular a-helix, all dipoles formed by the N-H .. . O-C main chain groups point along the helical axis

The a-helix is stabilized by the gain of hydrophobic energy when nonpolar side chains of amino acids are shielded from the solvent

According to Chothia (1976), when an a-helix is formed, the energy goes down by 2–3 kcal/mol per residue

Helices

Most a-helices are immersed into protein interior from one side and form an exterior protein surface from the other side

Analysis has shown that nonpolar residues are usually located on one side of a-helix (forming a hydrophobic cluster) and polar and charged residues are on the other side

3.10-helical conformation is relatively common in proteins. The 3.10-helix contains 3 residues and 10 main chain atoms per turn

Helices with internal hydrogen bonds in proteins

(A) 3.10-helix; (B) a-helix.

Beta Strands

About 36 percent of amino acid residues in globular proteins are in b-state

The phi and psi main chain angles of the b-structure are spread widely in the upper left corner of the Ramachandran plot

Phi = Psi = 180 ˚ corresponds to the allowed conformation and represents the fully extended conformation of the polypeptide chain

When looking along the polypeptide framework, one can see that the neighboring side chain groups are pointing to the opposite directions

However, such fully extended conformation is favorable for polyglycine only.

In the presence of other amino acids, the phi and psi angles are slightly different

Beta Strands

Maximum H bonding between the C=O and N-H groups of the main chain. There are two possible mutual arrangements of b strands in the b-sheet with respect to polypeptide chain direction: parallel and antiparallel

Turns 60° per two residues

The twist in b structure allows for conformational stabilization, providing energetically favorable contacts between the side chains of neighboring b-strands and the optimal orientation of the hydrogen bonds

Val, Ile, Tyr, and Thr -Mostly preferredGlu, Gln, Lys, Asp, Pro, and Cys -Rarely found

Beta Strands

(A) b-strand geometry; (B) Interacting b-strands

(A) Antiparallel b-sheet; (B) Parallel b-sheet

Beta Strands

Beta Strands : A more clear picture

Beta Turns

b-turn accounts for nearly 32 percent of all amino acid residues

b-turn is a polypeptide fragment comprised of four consecutive amino acid residues in a region where the polypeptide chain changes direction roughly 180 °

b-turns are usually located on the protein surface and contain many polar and charged amino acid side chains

Most turns contain glycine in the second or third position, where the absence of a side chain in glycine is favorable for the interaction among main chain atoms

Proline often occurs at the second position of turns. About two-thirds of Pro-Gly and Pro-Asp sequences in proteins with known 3D structures are located in the two middle residues of b-turns

Many b-turns connect neighboring fragments of secondary structures (a-a, a-b, and b-b)

Beta Turns

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