Patrick

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Patrick An Introduction to Medicinal Chemistry
3/e Chapter 6 PROTEINS AS DRUG
TARGETS RECEPTOR STRUCTURE SIGNAL
TRANSDUCTION Part 3 Section 6.7
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Contents Part 3 Section 6.7 4. Tyrosine
kinase linked receptors 4.1. Structure 4.2. Reac
tion catalysed by tyrosine kinase 4.3. Epidermal
growth factor receptor (EGF- R) (2
slides) 4.4. Insulin receptor (tetrameric
complex) 4.5. Growth hormone receptor 4.6. Signa
lling pathways (5 slides) 9 slides
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4. Tyrosine kinase linked receptors

• Bi-functional receptor / enzyme
• Activated by hormones
• Over-expression can result in cancer

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4. Tyrosine kinase linked receptors
4.1 Structure
Extracellular N-terminal chain
Intracellular C-terminal chain
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4. Tyrosine kinase linked receptors
4.2 Reaction catalysed by tyrosine kinase
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4. Tyrosine kinase linked receptors
4.3 Epidermal growth factor receptor (EGF- R)
Induced fit opens tyrosine kinase active sites
Link
Link
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Link
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4. Tyrosine kinase linked receptors
4.3 Epidermal growth factor receptor (EGF- R)

• Active site on one half of dimer catalyses
  phosphorylation of Tyr residues on other half
• Dimerisation of receptor is crucial
• Phosphorylated regions act as binding sites for
  further proteins and enzymes
• Results in activation of signalling proteins and
  enzymes
• Message carried into cell

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4. Tyrosine kinase linked receptors
4.4 Insulin receptor (tetrameric complex)
Kinase active site opened by induced fit
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http//www.vivo.colostate.edu/hbooks/pathphys/endo
crine/moaction/surface.html
Link
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4. Tyrosine kinase linked receptors
4.5 Growth hormone receptor Tetrameric complex
constructed in presence of growth hormone
Kinase active site opened by induced fit
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4. Tyrosine kinase linked receptors
4.6 Signalling pathways
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4. Tyrosine kinase linked receptors
4.6 Signalling pathways
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4. Tyrosine kinase linked receptors
4.6 Signalling pathways
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4. Tyrosine kinase linked receptors
4.6 Signalling pathways
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4. Tyrosine kinase linked receptors
4.6 Signalling pathways
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http//www.bioinformaticscourses.com/ISB/sp2003/1F
MK/mechanism.html
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http//faculty.plattsburgh.edu/donald.slish/tyrosi
nekinase/TK1.html
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Assigned Reading An Introduction to Medicinal
Chemistry by Graham Patrick, Chapter 6, pp
90-116.
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Homework Questions Briefly describe the three
different families of membrane-bount receptors,
including the relative speed of signal
transduction. Briefly describe the mechanism
whereby a typical GPCR exerts its effect.