AVS 271 Anatomy and Physiology

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AVS 271 Anatomy and Physiology

• Handout 3
• September 3, 2008
• Protein Activity

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The ability of various molecules and ions
to bind to specific sites on the surface
of a protein forms the basis for the wide
variety of protein functions that are
important in most physiological processes
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Protein Binding Characteristics

• Ligand
• Any molecule or ion that binds to the
  surface of a protein
• E.g., hormones (protein, steroid, etc.),
  minerals (calcium, etc)
• Binding site
• The specific region of the protein to
  which a ligand binds
• Determined by its 3 D conformation (i.e.,
  shape)

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Factors that influence ligand binding

• Chemical specificity
• Affinity
• Saturation
• Competition

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Chemical Specificity

• For a ligand to bind to a protein, the
  ligand must be close to the protein
  surface
• Close proximity occurs when the shapes are
  complementary
• Like the pieces of a jigsaw puzzle
• Proteins with different amino acid sequences
  have different shapes
• different shaped binding sites

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Chemical Specificity
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Chemical Specificity
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Chemical Specificity
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Affinity

• The strength of ligand protein binding
• Determines how likely it is that bound
  ligand will become unbound
• High affinity or low affinity binding
• Factors that affect affinity
• Chemical specificity (i.e., shape)
• Chemical charge(s) of both the ligand and
  the protein

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Affinity
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Saturation

• The fraction of total binding sites that
  are occupied at any given time
• Factors that affect saturation
• Concentration of unbound ligand in solution
• Affinity of the binding site for the ligand

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Saturation Effect of Ligand
Concentration(fixed number of binding sites)
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Saturation Effect of Affinity(fixed
number of binding sites and ligand)
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Competition

• Occurs when more than one ligand can bind
  to a single binding site
• The presence of more than one ligand able
  to bind to the same site affects the
  percentage of binding sites occupied by any
  one ligand

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Competition
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Regulation of Binding Site Characteristics

• Two ways of controlling protein activity
• Changing the shape of a protein
• Alters ligand binding
• Allows rapid (i.e., immediate) control of
  protein activity
• Regulating protein synthesis and degradation
• Determines the type and amount of proteins
  that are present
• Slower (i.e., delayed) method of controlling
  protein activity

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Altering Protein Shape

• Allosteric modulation
• Covalent modulation

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Allosteric Modulation

• Whenever a ligand binds to a protein, the
  attracting forces alter the proteins shape
• As the shape of the binding site changes,
  it changes the shape in other regions of
  the protein
• For proteins with multiple binding sites
• Binding at one site can alter the shape
  of other binding sites
• Regulatory binding site
• Modulator molecule
• Functional binding site

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Allosteric Modulation
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Allosteric Modulation
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Covalent Modulation

• Covalent bonding of charged chemical groups
  to a protein
• Generally, a phosphate group (neg. charge)
  is added via a phosphorylation reaction
• Protein kinase
• Any enzyme that mediates protein
  phosphorylation
• Very specific
• Phosphoprotein phosphatase
• Any enzyme that mediates removal of a
  phosphate group (i.e., dephosphorylation)
• Relatively non specific

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Covalent Modulation
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Covalent Modulation
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