proteins: three-dimensional structure

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Proteins: Three-dimensional Proteins: Three-dimensional structure structure Background on protein composition Background on protein composition : : Two general classes of proteins Two general classes of proteins - long rod-shaped, insoluble proteins. - long rod-shaped, insoluble proteins. These proteins are strong (high tensile strength). These proteins are strong (high tensile strength). Examples: keratin, hair, collagen, skin nails etc… Examples: keratin, hair, collagen, skin nails etc… - compact spherical shaped proteins - compact spherical shaped proteins usually water-soluble. Most hydrophobic amino usually water-soluble. Most hydrophobic amino acids found in the interior away from the water. acids found in the interior away from the water. Nearly all enzymes are globular… an example is Nearly all enzymes are globular… an example is hemoglobin hemoglobin

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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… - PowerPoint PPT Presentation

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Page 1: Proteins: Three-dimensional structure

Proteins: Three-dimensional Proteins: Three-dimensional structurestructureBackground on protein compositionBackground on protein composition::

Two general classes of proteinsTwo general classes of proteins - long rod-shaped, insoluble proteins. These - long rod-shaped, insoluble proteins. These

proteins are strong (high tensile strength). Examples: proteins are strong (high tensile strength). Examples: keratin, hair, collagen, skin nails etc…keratin, hair, collagen, skin nails etc…

- compact spherical shaped proteins usually - compact spherical shaped proteins usually water-soluble. Most hydrophobic amino acids found in the water-soluble. Most hydrophobic amino acids found in the interior away from the water. Nearly all enzymes are interior away from the water. Nearly all enzymes are globular… an example is hemoglobinglobular… an example is hemoglobin

Page 2: Proteins: Three-dimensional structure

Proteins: Three-dimensional Proteins: Three-dimensional structurestructureBackground on protein compositionBackground on protein composition::

Two general classes of proteinsTwo general classes of proteins FibrousFibrous - - long rod-shaped, insoluble proteins. These proteins long rod-shaped, insoluble proteins. These proteins

are strong (high tensile strength). Examples: keratin, hair, are strong (high tensile strength). Examples: keratin, hair, collagen, skin nails etc…collagen, skin nails etc…

- compact spherical shaped proteins usually - compact spherical shaped proteins usually water-soluble. Most hydrophobic amino acids found in the water-soluble. Most hydrophobic amino acids found in the interior away from the water. Nearly all enzymes are interior away from the water. Nearly all enzymes are globular… an example is hemoglobinglobular… an example is hemoglobin

Page 3: Proteins: Three-dimensional structure

Proteins: Three-dimensional Proteins: Three-dimensional structurestructureBackground on protein compositionBackground on protein composition::

Two general classes of proteinsTwo general classes of proteins FibrousFibrous - long rod-shaped, insoluble proteins. These proteins - long rod-shaped, insoluble proteins. These proteins

are strong (high tensile strength). Examples: keratin, hair, are strong (high tensile strength). Examples: keratin, hair, collagen, skin nails etc…collagen, skin nails etc…

GlobularGlobular - - compact spherical shaped proteins usually water-compact spherical shaped proteins usually water-soluble. Most hydrophobic amino acids found in the interior soluble. Most hydrophobic amino acids found in the interior away from the water. Nearly all enzymes are globular… an away from the water. Nearly all enzymes are globular… an example is hemoglobinexample is hemoglobin

Page 4: Proteins: Three-dimensional structure

Proteins: Three-dimensional Proteins: Three-dimensional structurestructureBackground on protein compositionBackground on protein composition::

Two general classes of proteinsTwo general classes of proteins FibrousFibrous - - long rod-shaped, insoluble proteins. These proteins long rod-shaped, insoluble proteins. These proteins

are strong (high tensile strength). Examples: keratin, hair, are strong (high tensile strength). Examples: keratin, hair, collagen, skin nails etc…collagen, skin nails etc…

GlobularGlobular - - compact spherical shaped proteins usually water-compact spherical shaped proteins usually water-soluble. Most hydrophobic amino acids found in the interior soluble. Most hydrophobic amino acids found in the interior away from the water. Nearly all enzymes are globular… an away from the water. Nearly all enzymes are globular… an example is hemoglobinexample is hemoglobin

Proteins can be simpleProteins can be simple - - no added groups or modifications, just no added groups or modifications, just amino acidsamino acids

Or proteins can be conjugatedOr proteins can be conjugated.. Additional groups covalently Additional groups covalently bound to the amino acids. The naked protein is called the bound to the amino acids. The naked protein is called the apoprotein and the added group is the prosthetic group. apoprotein and the added group is the prosthetic group. Together the protein and prosthetic group is called the Together the protein and prosthetic group is called the holoprotein. Ex. hemoglobinholoprotein. Ex. hemoglobin

Page 5: Proteins: Three-dimensional structure

Four levels of protein Four levels of protein structurestructure

Primary structurePrimary structure:: amino acid only. The actual amino acid amino acid only. The actual amino acid sequence is specified by the DNA sequence. The primary sequence is specified by the DNA sequence. The primary structure is used to determine genetic relationships with other structure is used to determine genetic relationships with other proteins - AKA homology. Amino acids that are not changed are proteins - AKA homology. Amino acids that are not changed are considered invariant or conserved.considered invariant or conserved.

Primary Primary sequence is sequence is also used to also used to determine determine important important regions and regions and functions of functions of proteins - proteins - domains.domains.

Page 6: Proteins: Three-dimensional structure

Four levels of protein Four levels of protein structurestructureSecondary structureSecondary structure:: This level is only concerned with the local This level is only concerned with the local

or close in structures on the protein - peptide backbone. The or close in structures on the protein - peptide backbone. The side chains are not considered here, even though they have an side chains are not considered here, even though they have an affect on the secondary structure. affect on the secondary structure.

Two common Two common secondary secondary structures - structures - alpha helix and alpha helix and beta pleated beta pleated sheetsheetNon- regular Non- regular repeating repeating structure is structure is called a random called a random coil. coil. - no specific - no specific repeatable repeatable patternpattern

Page 7: Proteins: Three-dimensional structure

Four levels of protein structureFour levels of protein structureTertiary structureTertiary structure - the overall three-dimensional shape that a - the overall three-dimensional shape that a protein assumes. This includes all of the secondary structures protein assumes. This includes all of the secondary structures and the side groups as well as any prosthetic groups. This level and the side groups as well as any prosthetic groups. This level is also where one looks for native vs. denatured state. The is also where one looks for native vs. denatured state. The hydrophobic effect, salt bridgeshydrophobic effect, salt bridges

And other And other molecular molecular forces are forces are responsible responsible for for maintaining maintaining the tertiary the tertiary structurestructure

Page 8: Proteins: Three-dimensional structure

Four levels of protein Four levels of protein structurestructure

Quaternary structureQuaternary structure:: The overall interactions of The overall interactions of more than one peptide chain. Called subunits.more than one peptide chain. Called subunits.

Each of the sub Each of the sub units can be units can be different or different or identical identical subunits, subunits, hetero or hetero or homo – x homo – x mers (ex. mers (ex. Heterodimer Heterodimer is a protein is a protein composed of composed of two different two different subunits).subunits).

Page 9: Proteins: Three-dimensional structure

Secondary structure - detailsSecondary structure - detailsTo look at the secondary structure and understand why To look at the secondary structure and understand why

helices and sheets are formed we need to first look at helices and sheets are formed we need to first look at the nature of the peptide backbone.the nature of the peptide backbone.

- In organic chemistry the bond formed between a COOH and - In organic chemistry the bond formed between a COOH and NH3+ groups is called the amide. This is similar but different NH3+ groups is called the amide. This is similar but different from the peptide bond.from the peptide bond.

- The peptide bond if - The peptide bond if formed between the formed between the alpha carbon carbonic alpha carbon carbonic acid of one protein acid of one protein and the amine of and the amine of another alpha carbon. another alpha carbon. The difference is in The difference is in the increased double the increased double bond nature of the bond nature of the bond. There is lots of bond. There is lots of resonance and resonance and therefore no rotationtherefore no rotation

Page 10: Proteins: Three-dimensional structure

- A peptide bond can be thought of as a double bond with four atoms in A peptide bond can be thought of as a double bond with four atoms in a plane.a plane.

- The bonds on either side are freely rotatableThe bonds on either side are freely rotatable

- The bonds within the plane are fixed.The bonds within the plane are fixed.

- The amino acid side groups are usually in the trans conformation. The - The amino acid side groups are usually in the trans conformation. The exception is the proline amino acid.exception is the proline amino acid.

- Usually in the cis - Usually in the cis conformation- due to the conformation- due to the nature of the side group - nature of the side group - amine bond.amine bond.

SecondarySecondary structure - detailsstructure - details

Page 11: Proteins: Three-dimensional structure

Secondary structure - detailsSecondary structure - detailsThe conformation of the backbone is described as The conformation of the backbone is described as Torsion angles Torsion angles or or

rotational anglesrotational angles

Occur around the COccur around the Cphiphiand theand theCCC C psipsi

By convention these angles are both set as 180 when in the fully extended By convention these angles are both set as 180 when in the fully extended conformation conformation

When viewed form the When viewed form the CCthey are said to increase clockwisethey are said to increase clockwise

Page 12: Proteins: Three-dimensional structure

Rotational anglesRotational angles - - the two bonds which rotate around the the two bonds which rotate around the peptide bond are called the phi and psi (y and f). Called peptide bond are called the phi and psi (y and f). Called torsional anglestorsional angles

-Due to the crowded environment of a Due to the crowded environment of a peptide bond, these torsion angles exists peptide bond, these torsion angles exists in the lowest energy state conformation. in the lowest energy state conformation. That means that the bonds rotate That means that the bonds rotate without breaking the covalent bonds, without breaking the covalent bonds, usually by rotation.usually by rotation.

Page 13: Proteins: Three-dimensional structure

Ramachandran DiagramsRamachandran DiagramsPhi and Psi angles can be calculated!Phi and Psi angles can be calculated!

A Ramachandran plot shows the A Ramachandran plot shows the values of the torsional angles values of the torsional angles and allows prediction of the and allows prediction of the conformationconformation

Blue areaBlue area – shows sterically – shows sterically allowed Phi and Psi allowed Phi and Psi conformationsconformations

Green areaGreen area – sterically forbidden – sterically forbidden conformations – would bring conformations – would bring atoms closer than atoms closer than corresponding van der Waals corresponding van der Waals distancedistance

((distance of closest contact distance of closest contact between non-bound atomsbetween non-bound atoms))

Page 14: Proteins: Three-dimensional structure

Ramachandran DiagramsRamachandran DiagramsPhi and Psi angles can be calculated!Phi and Psi angles can be calculated!

The angle will depend on the two The angle will depend on the two amino acids. The steric amino acids. The steric hindrance between the hindrance between the functional groups determine the functional groups determine the angle of stability.angle of stability.

There are only limited means of There are only limited means of conformation the sheets and conformation the sheets and heliceshelices..

Right-handed alpha helix Right-handed alpha helix

Left-handed alpha helixLeft-handed alpha helix

Parallel beta sheetParallel beta sheet

Anti-parallel beta sheetAnti-parallel beta sheet

Collagen helixCollagen helix

Page 15: Proteins: Three-dimensional structure

And there are always And there are always exceptions!exceptions!

ProlineProline –Cyclic side chain limits the –Cyclic side chain limits the range of rotation range of rotation

It is the most conformationally It is the most conformationally restricted amino acid residue restricted amino acid residue

GlycineGlycine- The only amino acid without a - The only amino acid without a beta carbon atom is the smallest of beta carbon atom is the smallest of the amino acidsthe amino acids

Has almost unlimited rotational freedom Has almost unlimited rotational freedom and can fit into almost any and can fit into almost any conformationconformation