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VALINE Final Presentation (pertussis toxin)

HTH SCI 2E03: Biochemistry Inquiry
by

E C

on 13 June 2013

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Transcript of VALINE Final Presentation (pertussis toxin)

Team Valine
Dr. Werstuck's
Sukriti Bhardwaj
Erin Budd
Eric Cheng
Nicole Jedrzejko
Esaba Kashem
Yousif Kellow
Ellen Liang
Nicholas Timmerman
Sarah Xu
Pertussis Toxin
F Y G A A S S Y F E Y V D T Y G D N A G R I L A G A L A T Y Q S E Y L A H R R I
DISTRIBUTION
WHO, 2002
TRANSMISSION
COLONIZATION
Contagious
Airborne droplets
16 million cases
90% in developing areas
Increasing incidence
Tracheal cells
Filamentous hemagglutinin (FHA)
Biofilm
PERTUSSIS TOXIN
PTX acts on G-proteins
AB5 exotoxin
A protomer (catalytic)
B oligomer (binding)
AMINO ACID SEQUENCE
(S1 SUBUNIT)
SYNTHESIS & SECRETION
TRANSCRIPTION
BvgAS - 2 component system:
BvgS
(sensor kinase) &
BvgA
(transcription factor)
TRANSLATION
fMet = N-formyl + Met
Cleaved by peptide deformylase (PDF)
Metalloproteinase for maturation
Met aminopeptidase (MAP) removes met residue
TRANSPORT
SEC PATHWAY & ASSEMBLY
Leader peptide of preprotein:
Recognized by chaperone proteins
Guided to periplasm by preprotein translocase
Cleaved by LEP protein
Disulphide bonds
Glutathione
Ptl system
Creation of pore
ENDOCYTOSIS
Binds to ciliated trachea epithelial cells
Retrograde transport
No ERAD & ubiquitin
S1 dissociates (ATP & enzymes)
Attaches to plasma membrane

Glycoprotein/lipid receptors
S1's Glu129 attaches to NAD+ (dehydration)
S1's His35 deprotonates G's Cys351
Transfers ADP ribose onto alpha subunit (nucleophilic attack)
TREATMENT
vaccines & antibiotics
DTa
P
& Tda
p
Whole cell vs. acellular
14-atom lactone ring
Shorter half-life
More side effects
Most common
Derivative, with N
Less side effects
Improved ribosome affinity
Improved tissue penetration
Erythromycin
Azithromycin
VALINE'S RECOMMENDATION:
PDF inhibitors
Thank you!
- Team Valine
MACROLIDES -
prevent
peptide elongation
No resistance
Gram-negative infections
Bacteriostasis
HsPDF
LBM415
Bacterial
Cell
Host Cell
x-ray
crystallography
improves
immunity
Bordetella pertussis
Causes pertussis (whooping cough)
Gram-negative
Aerobic
Coccobacillus
Epidemiology
Transmission of bacteria
Colonization of bacteria
Introduction to PTX
Transcription (BvgAS system)
Translation
Secretion & Assembly
Transport & Exocytosis
Binding & Endocytosis
Retrograde Transportation
ADP Ribosylation
OUTLINE
PERTUSSIS
TOXIN PATHWAY
Vaccines
Antibiotics
Novel Treatment (PDF Inhibitors)
Conclusion
TREATMENT
IN BACTERIAL CELL
Hypoglycemia
Lymphocytosis
Histamine sensitization
ADP ribosylation
TOXIN PATHWAY
IN HOST CELL
RESISTANCE
LBM415
Full transcript