Transcript Powerpoint

Keep an in-class experiential diary today*
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If you have any food issues (allergies, reactions) don’t do
any of this, please. I know of no significant risk, but I get
paid less whenever someone dies before the drop date.
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Use a friend’s observations
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Try some diet DP. Record observations; focus on
sweetness
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Get a ‘lemon or lime kit’. When your mouth is totally free of
other tastes, you may ‘suck a citrus’. Leave one section
for later!!
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Record observations; await further instruction
*You’ll need it for the homework
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Oh, the weather outside
There’s more to protein folding, structure, activity
than just water & amino acid sequence.
And it matters.
Atom parts
Freeman, Biological Science, Fig. 2-1
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What’s this?
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What happens when its
electron gets ‘shared’ away?
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What happens when you...
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go outside and it’s raining?
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visit friends with a pet and not much cleaning up?
An experimental demonstration of consequence of pH
Step I: squeeze a lemon quarter into your mouth.
Mmmmm Mmmmm good!
A word on nomenclature
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Hydrogen concentrations can vary a lot--like,
1,000,000,000,000-fold
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Inconvenient! We speak of ‘puissance d’hydrogene’ (‘power
of hydrogen’, according to your text) or pH
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look to pure water (hydrogen ion concentration 10-7
molar), extract the exponent (10-7), positivize it &
declare ‘pH 7’
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Thus: pH = negative (logarithm of concentration H+ )
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i.e. pH = -log[H+]
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!
+
H
Watching
(from tiny to tons)
Relative
Clarity:
An acid gives up its
pH to become
negatively charged,
but the solution it’s
in gains an H+
1/10,000
Rarer free
1/1,000
H+
1/100
1/10
10x
100x
More free
H+
1,000x
10,000x
100,000x
1,000,000x
Fig 2.16
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Amino acid balances of power
Alert:
This is a poorly thought out color scheme.
Protons are more common at the bottom
(alas, shown as red)
Lysine sidechain 50% neutral
Histidine sidechain 50% positive
Glutamic acid sidechain 50% neutral
Fig 2.16
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Picking on Histidine
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Fill in: while carbon makes __A__ [#] bonds b/c it has
__B__ [#] outer shell electrons, nitrogen makes __C__
[#], oxygen _D_ [#]
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What are the 2 non-bonding electrons of nitrogen doing?
the 2 PAIR of non-bonding electrons in oxygen?
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How do those pairs ‘feel’?
http://forums.studentdoctor.net/showthread.php?t=770938
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Sidechain ‘behavior’
at pH 7, proton mostly gone.
negative charge
at pH 6, 1/2 neutral, 1/2
positive: in the balance!
at pH 7, proton mostly loaded.
positive charge
pKa: the concentration of protons (pH) at which 50%
of the group in question has an H+ on board
http://upload.wikimedia.org/wikipedia/commons/0/0f/Amino_acids.png
Note: the image is linked from the homepage ‘sources’ menu as ‘aa sidechains’
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But who cares? Does
pH matter?
Argument I: Ever heard of ‘the flu’ ?
Argument II: What happened to your lemon?
First, though...
ONCE the lemon sourness gone, suck on your pill.
Do not chew; goal is to coat tongue thoroughly
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Background
In the United States, seasonal influenza epidemics typically claim the lives of
about 30,000 people each year and cause hospitalization of more than 100,000
(Reid & Tautenberger, 2003). Every two or three years, more virulent strains
circulate, increasing death tolls by approximately 10,000 to 15,000 individuals*.
These seasonal epidemics are the result of antigenic drift, a phenomenon
caused by mutations in two key viral genes due to an error-prone RNA
polymerase.***
Clancy, S. (2008) Genetics of the influenza virus. Nature Education 1(1)
*The one in 1918 killed 50-100 million worldwide
***Being small, it can get away with a ‘lesser’ nucleic acid (RNA) as its genome
note that inevitable errors actually provide periodic advantage
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Outside cell
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Virus stick to cell surface protein
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Cell engulfs; creating vesicle
(‘endosome’; first step in eating)
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Cell seeks to destroy by pumping in
protons (cell thinks “I will destroy & eat!”)
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Virus fuses its membrane with vesicle,
releasing genome (RNA) into
cytoplasm!!!
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You sneeze for a week… or
(occasionally) die
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http://cbm.msoe.edu/
A molecular saboteur
http://www.rpc.msoe.edu/cbm/resources/HAAnimation.swf
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Harpoon!
pH 7
pH 5
http://www.rpc.msoe.edu/cbm/
currentprograms/curIHP.php
http://www.rcsb.org/pdb/education_discussion/molecule_of_the_month/download/Hemagglutinin.pdf
Where, what, when
http://www.mcb.uct.ac.za//cann/335/335Rep2.jpg
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So what?
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These are ways to influence a protein from without
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...and ways for a cell to respond to environment
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The rest of the demo
When the pill is all gone
--FIRST, have another swig of that delicious Diet DP!
--NEXT try your other lemon slice
What’s the difference? What has changed? What can
you infer
Assertion: pH + one or more histidines + stuff you can
think your way through
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You might also enjoy
pH
http://www.sumanasinc.com/webcontent/animations/content/influenza.html
http://www.callutheran.edu/BioDev/omm/jmol/ha/ha.html