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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 – PowerPoint PPT presentation

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Title: Patrick


1
Patrick An Introduction to Medicinal Chemistry
3/e Chapter 6 PROTEINS AS DRUG
TARGETS RECEPTOR STRUCTURE SIGNAL
TRANSDUCTION Part 3 Section 6.7
2
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
3
4. Tyrosine kinase linked receptors
  • Bi-functional receptor / enzyme
  • Activated by hormones
  • Over-expression can result in cancer

4
4. Tyrosine kinase linked receptors
4.1 Structure
Extracellular N-terminal chain
Intracellular C-terminal chain
5
4. Tyrosine kinase linked receptors
4.2 Reaction catalysed by tyrosine kinase
6
4. Tyrosine kinase linked receptors
4.3 Epidermal growth factor receptor (EGF- R)
Induced fit opens tyrosine kinase active sites
Link
Link
7
Link
8
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

9
4. Tyrosine kinase linked receptors
4.4 Insulin receptor (tetrameric complex)
Kinase active site opened by induced fit
10
http//www.vivo.colostate.edu/hbooks/pathphys/endo
crine/moaction/surface.html
Link
11
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
12
4. Tyrosine kinase linked receptors
4.6 Signalling pathways
13
4. Tyrosine kinase linked receptors
4.6 Signalling pathways
14
4. Tyrosine kinase linked receptors
4.6 Signalling pathways
15
4. Tyrosine kinase linked receptors
4.6 Signalling pathways
16
4. Tyrosine kinase linked receptors
4.6 Signalling pathways
17
http//www.bioinformaticscourses.com/ISB/sp2003/1F
MK/mechanism.html
18
http//faculty.plattsburgh.edu/donald.slish/tyrosi
nekinase/TK1.html
19
Assigned Reading An Introduction to Medicinal
Chemistry by Graham Patrick, Chapter 6, pp
90-116.
20
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.
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