Proteins and Amino Acids

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Biological Functions of Proteins• Facilitate biochemical reactions• Structural support• Storage and Transport• Immune protection• Generate movement• Transmission of nerve impulses• Control growth and differentiation

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Key Properties of Proteins

• Linear polymers of amino acids• Contains a wide range of functional groups• Forms complex assemblies of more than

one polypeptide chain• Versatile structure – some are rigid while

others are flexible

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Globular and Fibrous Proteins• Globular protein• Usually water soluble,

compact, roughly spherical

• Hydrophobic interior, hydrophilic surface

• Globular proteins include enzymes,carrier and regulatory proteins

• Fibrous protein• Provide mechanical support• Often assembled into large

cables or threads• α-Keratins: major components

of hair and nails• Collagen: major component of

tendons, skin, bones and teeth

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General Structure of Proteins• Twenty common a-amino acids have

carboxyl and amino groups bonded to the α-carbon atom• A hydrogen atom and a side chain (R) are

also attached to the α-carbon atom

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Zwitterions • Under normal cellular conditions amino

acids are zwitterions (dipolar ions):Amino group = -NH3+

Carboxyl group = -COO-

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Stereochemistry of amino acids• 19 of the 20 common amino acids have a

chiral a-carbon atom (Gly does not)

• Threonine and isoleucine have 2 chiral carbons each (4 possible stereoisomers each)

• Mirror image pairs of amino acids are designated L (levo) and D (dextro)

• Proteins are assembled from L-amino acids (a few D-amino acids occur in nature)

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Amino acid side chains

• Nine non-polar aa• Six polar uncharged aa• Five charged aa• Three basic aa• Two acidic aa• Two aa with sulfur groups• Four ring-forming aa• Three have aromatic rings 9

Hydropathy• Relative hydrophobicity of the

amino acid

• The larger the hydropathy, the greater the tendency of an amino acid to prefer a hydrophobic environment

• Hydropathy affects protein folding: hydrophobic side chains tend to be in the interiorhydrophilic residues tend to be on the surface

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Acid-base chemistry of amino acids

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Isoelectric point

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• pH at which the amino acid bears zero net charge

Titration curve of Histidine

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Polymer of amino acid• Peptide bond -

linkage between amino acids is a secondary amide bond

• Formed by condensation of the α-carboxyl of one amino acid with the α-amino of another amino acid (loss of H2O molecule)

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Resonance Structure of the peptide bond

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Trans and Cis configuration of peptide bond• Usually in the trans configuration

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Dihedral Angle

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Dihedral angle of proteins

• The phi angle is the angle around the -N-Cα- bond• The psi angle is the angle around the -Cα-C- bond• The omega angle is the angle around the -C1-N- bond (i.e.

the peptide bond)

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LEVELS OF PROTEIN STRUCTURE 19

Primary structure

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>2CQG:A|PDBID|CHAIN|SEQUENCEGSSGSSGVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDSGPSSG

Secondary Structure

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Alpha-helix

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Right-handed and Left-handed α-Helix

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Right-handed and Left-handed α-Helix

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Beta-sheet

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Determining 2o structure: Ramanchandran Plot

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Supersecondary structure: Motifs• Secondary

structures often group together to form a specific geometric arrangements known as motifs

• Since motifs contain more than one secondary structural element, these are referred to as super secondary structures 27

Domains• stable, independently folding, compact

structural units within a protein, formed by segments of the polypeptide chain, with relative independent structure and function distinguishable from other regions and stabilized through the same kind of linkages than the tertiary level

• Often each domain has a separate function to perform for the protein, such as:• Bind a small ligand• Spanning the plasma membrane

(transmembrane proteins)• Contain the catalytic site (enzymes)• DNA-binding (in transcription factors)• Providing a surface to bind specifically to

another protein• In some (but not all) cases, each domain in a

protein is encoded by a separate exon in the gene encoding that protein.

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Tertiary Structure

• Forces holding the tertiary (and higher order) structure together• Salt bridge• Covalent bond

(disulfide bridges)• Hydrophobic

interaction• Hydrogen bonding 29

Quaternary Structure

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Protein Folding

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