Proteins: Three-dimensional structure

1. 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 water-soluble. Most hydrophobic amino acids found in the interior away from the water. Nearly all enzymes are globular… an example is hemoglobin

2. 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 water-soluble. Most hydrophobic amino acids found in the interior away from the water. Nearly all enzymes are globular… an example is hemoglobin

3. 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 water-soluble. Most hydrophobic amino acids found in the interior away from the water. Nearly all enzymes are globular… an example is hemoglobin

4. 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 water-soluble. 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

5. 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.

6. 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

7. 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

8. 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).

9. 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

10. Secondarystructure - 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.

11. Secondary structure - details • The conformation of the backbone is described as Torsion angles or rotational angles • Occur around the Ca-N [phi] and theCa-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

12. 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.

13. 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)

14. 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

15. 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