Biomacromolecules

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Biomacromolecules

• Pt IV Proteins

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Proteins

• Virtually everything a cell is or does depends
  upon the proteins it contains.
• Protein molecules carry out essential cellular
  functions and form the basis of many cell
  structures.
• Proteins show enormous functional diversity
  most proteins have one specific function.
• Easiest way to recall the different functions is
  to remember your
• TEACHERS

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TEACHERS

• T is for transport proteins which carry other
  molecules e.g. haemoglobin
• E is for enzymes which catalzye reactions e.g.
  ATP synthase
• A is for antibodies which are involved in
  defence against disease
• C is for contractile proteins which are involved
  in movement e.g. actin and myosin
• H is for hormones which regulate body activity
  e.g. insulin
• E is for exported proteins
• R is for receptors which respond to stimuli e.g.
  insulin receptors
• S is for structural proteins e.g. collagen and
  keratin

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What are proteins?

• Are macromolecules composed of linear polymers
  called polypeptides.
• Polypeptides are formed by condensation
  polymerisation of monomers called amino acids.
• Amino acids are essential biomolecules, not only
  because they are the building blocks of all
  proteins, but because they are a source of
  nitrogen for many other biomolecules including
  nucleotides, neurotransmitters and porphyrins.
• All proteins in life forms on Earth are formed
  from a set of 20 amino acids.
• Most micro-organisms can synthesise the complete
  set of 20 amino acids, whereas humans can only
  make 11.
• The remaining amino acids must be supplied from
  the diet and are called essential amino acids.

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Atoms in proteins

• Proteins contain five different types of atoms.
• This is remembered using the acronym
• SONCH
• Sulfur, Oxygen, Nitrogen, Carbon, Hydrogen

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Amino acids

• Amino acids have the same basic structure.
• There is an amino group (NH2), a carboxyl group
  (COOH) and an R group.
• The different chemical properties of individual
  amino acids are due to the atoms that make up the
  R group.
• The nature of the R side chain is important in
  determining the final functional shape of the
  protein.

• In neutral aqueous solutions such as the cell
  cytosol, amino acids exist in an ionized form.
  The acid group donates a proton (H) to the NH2,
  resulting in a dipolar ion called a zwitterion.

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R groups

• The R group can vary from simply one H in the
  case of glycine, to complex ring structures in
  the case of tyrosine.
• The R group contains atoms such as carbon,
  hydrogen, nitrogen and oxygen, and one amino acid
  (cysteine) contains sulphur.
• Nine amino acids have non-polar R groups (made up
  of hydrogen and carbon atoms) and are
  hydrophobic.
• The remaining eleven amino acids have polar R
  groups (largely due to the presence of oxygen)
  and are hydrophilic.
• Hydrophilic amino acids will tend to be on the
  surface of proteins because of their affinity
  with the polar water molecules in the cell
  environment.
• Hydrophobic amino acids will tend to be localized
  in the interior of the protein molecule away from
  water molecules.

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Polypeptides

• Macromolecules formed by linking amino acid
  monomers to form linear unbranched chains.
• A peptide bond is formed between the amino group
  on one amino acid and the carboxyl group of
  another in a process known as condensation
  polymerisation.

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Terminology of polypeptides

• A polypeptide chain has an unlinked amino group
  at one end, called the N-terminus, and an
  unlinked acid group at the other, called the
  C-terminus.
• By convention the N-terminal amino acid is
  depicted on the left and the C-terminal carboxyl
  group is on the right.
• When amino acids are linked by peptide bonds they
  are called amino acid residues.
• Chains of less than 20-30 residues are called
  peptide chains.
• Chains of more than 20-30 residues are called
  polypeptides.
• The term protein is usually reserved for a
  polypeptide (or complex of polypeptides) that has
  a three-dimensional shape.
• The size of a protein or polypeptide is reported
  in daltons. The size of the average amino acid
  is 110 daltons.

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Monomeric and multimeric proteins

• A protein is a polypeptide chain or several
  polypeptide chains that have achieved a unique,
  stable, three-dimensional structure and as a
  result of the final structure have biological
  functionality.
• Monomeric proteins
• Consist of only one polypeptide
• Achieve their final shape as a result of the
  folding and coiling of the polypeptide as it is
  formed.
• Multimeric proteins
• Consist of two or more polypeptide chains
• Final shape of the protein results not only from
  the folding and coiling of each polypeptide but
  also due to the interactions between the
  polypeptide chains.

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Haemoglobin is a multimeric protein

• Haemoglobin is an abundant protein in red blood
  cells that contains two copies of a globin and
  two copies of b globin.
• Each of these four polypeptide chains contains a
  heme molecule (red), which is the site where
  oxygen (O2) is bound.
• Each molecule of hemoglobin in the blood carries
  four molecules of oxygen.

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Levels of protein structure

• Primary structure
• Secondary structure
• Tertiary structure
• Quaternary structure

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Primary structure

• The sequence of amino acids that make up the
  polypeptide.
• Simply refers to the order of each amino acid
  from the N terminus to the C terminus of the
  polypeptide.
• The order of amino acids in a polypeptide is
  genetically determined.
• Three amino acids of importance structurally are
• Cysteine R side chain contains a sulfur atom
  that can bond with another sulfur molecule in an
  adjacent molecule to form a disulfide bond.
• Proline R side chain is a cyclic ring. This
  makes it very rigid and results in a fixed kink
  in a polypeptide chain.
• Glycine R side chain is a single H atom making
  glycine the smallest amino acid, and therefore
  able to fit into tight spaces.

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Secondary structure

• Different parts of a polypeptide assume different
  geometric arrangements due to interactions
  between amino acid residues.
• These interactions stabilise the backbone of the
  polypeptide producing three types of secondary
  structure
• alpha helix
• beta sheet
• random coils
• Secondary structure is a predictable repeating
  pattern, due to hydrogen bonding between peptide
  bonds.

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Secondary structure

• Alpha helix
• coils formed due to H bonds between O on one
  amino acid residue and the amide H on the next
  amino acid
• Beta sheet
• Folds perpendicular to the plane of the sheet.
• Stabilised by H bonds.
• May be intramolecular or intermolecular.
• Random coils
• Any portion of a polypeptide that does not show
  alpha helices or beta sheets is termed a random
  coil.
• Random coils are commonly found making up the
  active sites of enzymes.

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Tertiary structure

• Folding of the polypeptide chain that results in
  a stabilised overall three-dimensional shape
  called the conformation.
• Depends upon the R-group of each amino acid
  residue.
• Final shape is determined by competing
  interactions between the R groups, each with
  different properties.

• Covalent bonds form between sulfur molecules in
  adjacent cysteine residues.
• Hydrophobic R groups will associate together and
  seek out a non-aqueous environment.
• Hydrophilic R groups will associate together and
  be drawn to an aqueous environment.

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More about tertiary structure

• Proteins can be divided into two broad groups
  based on their tertiary structure fibrous
  proteins and globular proteins.
• Fibrous proteins
• Have extensive alpha helixes or beta sheets,
  giving them a highly ordered repetitive
  structure.
• In these proteins the secondary structure is more
  important than the tertiary structure as they
  have an extended filamentous structure.
• Examples of fibrous proteins are fibroin (silk)
  and keratins (hair, wool) as well as collagen (in
  skin) and elastin (ligaments and blood vessels).
• Globular proteins
• Have polypeptides folded into compact shapes
  rather than extended filaments.
• Within the compact shape are regions of alpha
  helixes and regions of beta sheets interspersed
  with random coils,
• These irregular structured regions allow the
  polypeptide chain to loop and fold thus giving
  the protein its functional shape or conformation.
  
• Most proteins involved in cellular functions are
  globular proteins e.g. haemoglobin.

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Quaternary structure

• Is only present in a protein if it is made up of
  more than one polypeptide chain.

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LEVEL OF ORGANISATION STRUCTURAL FEATURES TYPES OF BONDS AND INTERMOLECULAR INTERACTIONS
Primary Linear sequence of amino acids. Covalent peptide bond linking amino acid residues.
Secondary Coiling into helices and folding into sheets in parts of the polypeptide chain. Non-folded regions are called random coils. Hydrogen bonding.
Tertiary Folding of the polypeptide resulting in a 3D shape that is stabilised by various intermolecular interactions. Hydrogen bonds. Ionic bonds. Van der Waals interactions. Hydrophobic interactions. Disulfide bonds.
Quaternary Association of two or more folded polypeptides to form a protein. Ionic bonds. Van der Waals interactions. Hydrophobic interactions. Disulfide bonds.