1

❖ 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.

❖ Use a friend’s observations

❖ Try some diet DP. Record observations; focus on sweetness

❖ 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!!

❖ Record observations; await further instruction

Keep an in-class experiential diary today*

*You’ll need it for the homework

2

Oh, the weather Oh, the weather outsideoutside

There’s more to protein folding, structure, There’s more to protein folding, structure, activity than just water & amino acid activity than just water & amino acid

sequence.sequence.And it And it mattersmatters..

3

Atom parts

❖ What’s this?

❖ What happens when its electron gets ‘shared’ away?

Freeman, Biological Science, Fig. 2-1

4

What happens when you...

❖ go outside and it’s raining?

❖ visit friends with a pet and not much cleaning up?

An experimental demonstration of consequence of pHStep I: squeeze a lemon quarter into your mouth.

Mmmmm Mmmmm good!

5

A word on nomenclature❖ Hydrogen concentrations can vary a lot--like,

1,000,000,000,000-fold

❖ Inconvenient! We speak of ‘puissance d’hydrogene’ (‘power of hydrogen’, according to your text) or pH

❖ look to pure water (hydrogen ion concentration 10-7 molar), extract the exponent (10-7), positivize it & declare ‘pH 7’

❖ Thus: pH = negative (logarithm of concentration H+ )

❖ i.e. pH = -log[H+]

7Watching H+

(from tiny to tons)

Fig 2.16

10x

100x

1,000x

10,000x

100,000x

1,000,000x

1/10

1/100

1/1,000

1/10,000

Relative

More free H+

Rarer free H+

Clarity:An acid gives up its pH to become

negatively charged, but the solution it’s in

gains an H+

!

8Amino acid balances of power

Fig 2.16

Histidine sidechain 50% positive

Glutamic acid sidechain 50% neutral

Lysine sidechain 50% neutral

Alert:This is a poorly thought out color

scheme. Protons are more common at the

bottom(alas, shown as red)

9Picking on Histidine

❖ Fill in: while carbon makes __A__ [#] bonds b/c it has __B__ [#] outer shell electrons, nitrogen makes __C__ [#], oxygen _D_ [#]

❖ What are the 2 non-bonding electrons of nitrogen doing? the 2 PAIR of non-bonding electrons in oxygen?

❖ How do those pairs ‘feel’?

http://forums.studentdoctor.net/showthread.php?t=770938

10Sidechain ‘behavior’

http://upload.wikimedia.org/wikipedia/commons/0/0f/Amino_acids.png

Note: the image is linked from the homepage ‘sources’ menu as ‘aa sidechains’

pKa: the concentration of protons (pH) at which 50% of the group in question has an H+

on board

at pH 7, proton mostly gone.

negative chargeat pH 6, 1/2 neutral, 1/2 positive: in the

balance!at pH 7, proton mostly

loaded.positive charge

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But who cares? Does But who cares? Does pH pH mattermatter??

Argument I: Ever heard of ‘the flu’ ?Argument I: Ever heard of ‘the flu’ ?

Argument II: What happened to your lemon?Argument II: What happened to your lemon?

12First, though...

ONCE the lemon sourness gone, suck on your pill.Do not chew; goal is to coat tongue thoroughly

13Background

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.***

***Being small, it can get away with a ‘lesser’ nucleic acid (RNA) as its genome

note that inevitable errors actually provide periodic advantage

Clancy, S. (2008) Genetics of the influenza virus. Nature Education 1(1)

*The one in 1918 killed 50-100 million worldwide

14

http://cbm.msoe.edu/

❖ Virus stick to cell surface protein

❖ Cell engulfs; creating vesicle (‘endosome’; first step in eating)

❖ Cell seeks to destroy by pumping in protons (cell thinks “I will destroy & eat!”)

❖ Virus fuses its membrane with vesicle, releasing genome (RNA) into cytoplasm!!!

❖ You sneeze for a week… or (occasionally) die

Outside cell

15A molecular saboteur

http://www.rpc.msoe.edu/cbm/resources/HAAnimation.swf

16Harpoon!

http://www.rpc.msoe.edu/cbm/currentprograms/curIHP.php

pH 7 pH 5

http://www.rcsb.org/pdb/education_discussion/molecule_of_the_month/download/Hemagglutinin.pdf

17Where, what, when

http://www.mcb.uct.ac.za//cann/335/335Rep2.jpg

18So what?

❖ These are ways to influence a protein from without

❖ ...and ways for a cell to respond to environment

19The 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

20

You might also enjoyYou might also enjoypHpH

http://www.sumanasinc.com/webcontent/animations/content/influenza.http://www.sumanasinc.com/webcontent/animations/content/influenza.htmlhtml

http://www.callutheran.edu/BioDev/omm/jmol/ha/ha.htmlhttp://www.callutheran.edu/BioDev/omm/jmol/ha/ha.html