Welcome to my blog

Signaling 1

Some general outlines of ideas.

Na/K pump and gradients

I would like you to read David G’s really nice blog on the pump. I think you will find some of the numbers, frankly, shocking. Also, understanding the way this works will help you with other proteins we consider.
For example, some may be interested in proton pumps in the cells of the stomach that make the stomach acidic...it works like this protein, as David explains.

There are a few main points from today and I want you to be thinking how what we learned could be more generally applied in your thinking. Proceeding from specific to general:

The Pump

  • This protein has binding sites for ions. Below is an image of two ions bound. In this case, the protein crystallographers have used a trick and bound Rubidium+ to the sites. But, it works similarly. What would bind a positive ion? Well, you should hold it between negative ions, like deprotonated acid side chains. What are the acid side chains in amino acids?: Aspartic Acid (D) and Glutamic Acid (E). Look at the image below:

  • IonBindinginPump
  • D804, E327 and E779 (the numbers correspond to the residue number in the amino acid sequence, or primary structure) all come together to make a really nice pocket that binds the ions (greenish). That makes sense. There are others I didn’t label. All three residues that bind the cation are on different helices. If you slide those helices relative to each other, the components of the binding site move closer or farther away from each other. Now, check out the ionic radii of Na+ and K+ at the wikipedia page. K+ is 30% bigger than Na+ (Rb+ is only slightly larger than K+). So, by sliding the helices, I can change the sized of the pocket and whether K+ or Na+ is favored.
  • ATP hydrolysis transfers a phosphate to a serene on the pump (Serine 33 on our pump), causing the helices to shift. This opens the pump to the outside and changes the shape of the binding pocket so that Na+ cannot really be held tightly anymore and K+ fits in well.
  • The Binding of K+ changes the shape a little more. This favors hydrolysis of the phosphate from the serine, shifts the helices back to be open inside the cell and makes the pocket too small for K+, but allows Na+ back in. Of course, I didn’t explain exactly, but the three Na+ sites only reconstruct 2 K+ sites once the helices move.

This type of pump could be modified to pump other cations.

  • As Goodsell points out, this same mechanism can be used to pump protons. You just have to change the size of the binding pocket. That probably just involves some shifting of the positions of the acidic residues.

Gradients are useful

  • Once you establish a gradient, you can use it to do stuff. The pump establishes an electrochemical gradient. Every cell at “resting potential” has more K+ on the inside and more Na+ on the outside. The inside is also more negative. Maybe I could use that gradient to do something.
  • For example, suppose I had a protein that would allow Na+ to come back in...but it would only do that if there was also a glucose molecule bound. I could use the gradient to transport glucose into the cell.
  • Suppose I had a channel that I opened in response to some signal...maybe something binding to the channel, and that channel would allow sodium to pass through it. All the sodium ions would start racing into the cell, down their chemical gradient. But that would also make the inside positively charged...that would be a dramatic effect. It get’s even more complicated, but that’s the start of an action potential in nerve cells.
  • Or...what if I stacked a whole bunch of cells on top of one another and made a little battery of cells, each with a small voltage across the membrane...then released all of them at once. That would be really interesting.
  • Phosphorylation and interactions with other molecules change the shape of proteins

  • A more general mechanism exists by which any protein could have a set of possible shapes, each favored under different conditions. Imagine a protein that binds to microtubules, for example. Maybe you could come up with a series of shapes that change depending on whether ATP is bound, or ADP is bound, or the protein is bound to tubulin or not... Could you imagine a series of steps like: Bind ATP and Release from tubulin; hydrolyze ATP and move forward; bind again, release ADP....what would that look like?

Cells Intro

Basic stuff about cells. You will go much deeper in your project. Read More...

Protein Structure II

A bit more advanced stuff.

Intro Protein

Protein Structure: Overview

Amino Acids

You should know the basic structure of one, identify the amine, the alpha carbon, the “R” side chain and the carboxyl group (acid). You don’t need to name and recognize side chains. However, given an example, I would like you to be able to identify whether it is hydrophobic or what other important functional groups it has. Example: presented with serine:
you should be able to spot that the side-chain has an OH (top) on it. You could guess that it is a decent H-bond donor. You might also ask whether that OH is ever chemically attacked by a phosphate (it is, quite often).

Primary structure

Primary structure is nothing other than the sequence of amino acids that make up the proteins. While I don’t want you to sit and memorize the structures (well, I kind of do, but it’s a lot of memorization), I do want you to get to know the categories as they are identified in the book or at wikipedia. We haven’t gone into that yet. So far we have ignored the “R” groups.
Primary structure just gives you one long chain, like the chain of magnetic beads.
You should understand the chemistry of how amino acids connect to form peptides (dehydration synthesis). At typical peptide will include hundreds of amino acids. Notice that there is an
amino terminus and a carboxyl terminus. There are no actual amino acids left after peptide bond formation. They are then called “residues.”

Secondary Structure

Secondary structure is the first step of how the chain of amino acids folds. This does not directly involve the R groups, though, they will have an impact. The secondary structure will be due to hydrogen bonds between the carbonyl oxygen and the amine hydrogen of another residue. Those are part of the backbone.
For our purposes, there are two main secondary structures:
ɑ helices and β sheets (often called “beta pleated sheets,” by non biochemists).
Alpha helices will be like the small helices we built with the magnet spheres. There will not be enough space in the center of the helix for other molecules, even water, to fit. They are “right handed” screws. Looking down the spiral from either direction, the spiral runs clockwise away from you.
When we used the yellow models, we saw three main features:
  • The helix is held together by backbone hydrogen bonds between a carbonyl carbon and the amino group of the fourth amino acid along the chain.
  • This structure is fairly rigid.
  • This repeating structure places all the “R” side chains on the outside (they couldn’t fit in the center anyway). A subtle result of this is that residues 1, 4, 8 etc will be on the same side of the helix.
Here is a close up of a helix in the estrogen receptor
Notice the dotted lines indicating hydrogen bonds between a carbonyl in the backbone (little red sphere for oxygen) and the hydrogen of the amine on the loop in front of it. I have labeled two amino acids. There’s the ringed histadine (you probably are almost able to spot it by now) labeled H516 (that just means it’s the 516th amino acid residue in the primary structure. The one on the same side of the helix exactly one loop further to the right is Lysine 520 (K520). It’s four residues farther along.

Why do some amino acids form helices and some not?

The other common form of secondary structure is called a “beta sheet” or “beta pleated sheet.” (See below) Why do some chains form helices and some form sheets?

Dihedral angles:

Phi Psi Angles 1These angles, also known as the “phi/psi” angles denote the rotation around the N-Carbonalpha bond (phi, ϕ) or the rotation around the Carbonalpha-Carboncarbonyl bond (psi, ѱ)
The key thing to know is that, while the atoms are free to spin around the single bonds, there is a preferred dihedral angle. That is generally dictated by the nature of the R side chain. You can force any amino acid (except proline) into the correct angles for an alpha helix. But, some are better at it than others. Alpha helices form because they are strings of amino acids that prefer the correct phi/psi angles. If you have a run of these alpha-helix-preferring residues, they form quickly into the correct structure.
Beta sheets are made up of residues that prefer a slightly different dihedral angle. Again, any amino acid except proline can fit into a beta sheet. But, some residues are better at it.
Beta sheets will be like those flat sheets we made, or, at least the two strands we made, with the magnet spheres. As with the spheres, the sheet can be made either of antiparallel strands or of parallel ones. Also like the spheres, the details of the structure will be different in parallel and antiparallel sheets. However, the wonderful beads breakdown as a nearly perfect model at this point.

Intro Enzyme Kinetics

The bulk of this came from the AP blog. It’s been modified a bit for you... Read More...

Energy Review

Why do things happen?
When you think about it, this is one of those fundamental questions. Historically, answers have ranged from religious or superstitious to mechanistic. We, predictably, will try to come up with mechanistic rules. And, our answer will be tied up with the idea of energy. Things in a high-energy state will tend to move to a lower energy state, so that energy will become more evenly distributed. All of biology will follow the rules of thermodynamics. Energy rules. So, we must talk about what energy is.
This is pretty much my intro about "capacity to cause pain."
Things in a high-energy state will tend to move to a lower energy state, so that energy will become more evenly distributed.
Remember that.

A biological example

So, we know what energy is and that there is a tug-of-war, of sorts, between two ways to satisfy the tendency of energy to distribute more evenly. What does this have to do with Biology?
When we look at biological systems, we might be forgiven for seeing purpose and direction in how biological systems work. However, as we will see throughout the year, biological molecules follow the same rules that all other molecules do. The properties we will observe in proteins, DNA and carbohydrates will all derive from the energetic requirements of their components.
The second big point is that idea of doing work as energy follows it’s normal tendency to distribute. That is the secret to understanding how biological systems keep themselves organized and do work.

The energy tug of war

Energy will tend to distribute evenly, or randomly (entropy will increase). But, there are two competing ways for this to happen. Changes in the temperature of the system determines which of these two competing strategies will win. Biological systems take full advantage of this tug of war to achieve the remarkable complexity they display. Read More...


This covers the basics of DNA, most of the stuff from the chapter, and a little more. Read More...

A pH Question

Some of you have had issues with question 7 on the pH quiz. Here are some hints. Read More...

Why did our glucose look different from the one on the board?

Rita asked a question when we were building sugars and I promised I would take time to answer it. I thought I might as well post it, in case others were also wondering. Read More...


This blog, and the next couple, are actually from AP Bio. Read More...


Polymers of sugar

or, polysaccharides.
A monomer of sugar, with the empirical formula CH2O, is called a simple sugar. For our purposes, hexoses including glucose and fructose are most important here. Pentoses such as ribose in RNA and deoxyribose in DNA will be dealt with later.
Sugars have a carbonyl on one carbon and hydroxyls on the others. The carbonyl can be on the end (an aldose such as glucose), or not on the end (A ketose, such as fructose). We often draw them as a linear form. But, in water, they are not.

Sugar Cyclization.

Here is the linear form of glucose:
Pasted Graphic 8
and another view in ball-and-stick model.
Pasted Graphic 9
Carbon 1 is on the right, the carbonyl.
The cyclization is just a rearrangement of the atoms in the molecule. No atoms are lost (e.g. water is not released).
The dashed-line bonds are bonds that would go slightly back into the page and the dark wedge-shaped bonds would come forward out of the page, as indicated in the 3-d view.
The chemistry of the interaction, if you care, is that the carbonyl carbon is very electron poor (the brutish oxygen is stealing it’s electrons). The lone pairs on any of the alcohol (OH) group oxygens could in principle initiate a reaction with the carbonyl carbon (alcohols and aldehyde often react...so when you put sugar in solution, it reacts with itself). The most stable ring is formed when the OH on Carbon 5 attacks the carbonyl carbon. As the bonds are exchanging, that oxygen ends up bridging carbon 1 and carbon 5 AND having a hydrogen bonded to it….This intermediate is unstable. Both the oxygen and Carbon 1 are making too many bonds, which cannot stay. So carbon 1 has to lose one bond to what had been the carbonyl oxygen. That leaves the carbon looking good, but we have one oxygen (in the ring) with 1 too many bonds (+1 formal charge) and the other on carbon one with not enough bonds (-1 formal charge). The more stable structures trades the hydrogen off the ring oxygen on (originally from carbon 5) to the former carbonyl carbon on carbon 1.
For those keeping score, this adds one more asymmetric carbon (carbon 1) and one more possible isomer, which we call the alpha and beta form, as we see in either starch or cellulose.
It seems like such a small thing: does the OH on carbon 1 stick straight out of the plane of the ring (called “axial”) as below:
Pasted Graphic 7
Or does it stick out more in plane with the ring (“equatorial”), as it does in this form:
Pasted Graphic 10

But, it is a big deal. The top form is called alpha and the bottom is called beta.


Polymerization is carried out by an enzyme that joins the joins carbon 1 of one ring with carbon 4 of another. It’s a dehydration synthesis, resulting in the OH from carbon 4 leaving with an H from the hydroxyl on the carbon 1 to form water. The bond can be hydrolyzed by a different enzyme. I said, animals lack the enzymes to deal with the beta form of glucose…But, actually, I was wrong about that, to some extent. We do have a (poor) beta glucosidase…in our tears. It’s called “lysozyme” and it’s part of our defense against bacteria. Also, a sugar similar to glucose (another hexose/aldose with the formula C
6H12O6) called galactose pairs in its beta form with glucose to form a disaccharide called Lactose (perhaps you’ve heard of it?). At least as infants, we make a beta galactosidase protein called “lactase.” Most of us don’t make that when we get older and so we have some level of lactose intolerance.

But, in general, we deal poorly with beta forms of glucose in polymers.

Pasted Graphic 3
This is a representation of cellulose (also known as “Fiber”) from Wikipedia, the same one we looked at today. It is a main structural component of plants, in what is known as the “cell wall”. Note that there are four VERY short chains linked through the oxygens in a beta 1-4 link. The actual chains would be much longer.
Notice that the oxygen on carbon 1 (right-hand carbon in each ring) is sticking out to the side of the ring. The net result of this is that the sugars alternate orientation. You can see this best by looking at the carbon 6, which is sticking out of the rings, either up or down, alternating.
As a result of this, there are hydrogen bonds both within each chain (from each sugar to the next) and to the chain running along side of it. Seems like a recipe for something fairly strong, but flexible (chains can slide along each other under stress, simply making new hydrogen bonds).
This is a great example of how details of the fine structure explain the behavior of the larger structure. Wood is essentially made of single fibers all cross-linked in many directions that allows at least some sliding, and therefore bending.

Compare it to this, which is starch (we can digest that).

Pasted Graphic 5
In this case, you see the O off carbon 1 sticking down, out of the plane of the ring. This leads to all the sugars more or less orienting the same way, no great ability for hydrogen-bond cross linking, and sort of a slow, spiraling of the strand.

Key properties of polysaccharides for AP:
  1. Cellulose and Starch (and the slightly branched “amylopectin”) are made by plants.
  2. Glycogen is made in animals (mainly in the liver).
  3. Starch, pectin and glycogen all use alpha glucose and are mainly storage forms of glucose. Your body, for example, will either make or hydrolyze glycogen to take up or release glucose to your blood.
  4. Cellulose is the beta form of glucose and used primarily to provide structure.
  5. Though a strand of polysaccharide is joined from carbon 1 of a glucose to carbon 4 of the next, you can have branching where a long strand will attack carbon 6 (the one outside the ring) with its carbon 1.
  6. Cellulose has no branching; starch (amylose) has no branching and pectin a little branching. Glycogen is highly branched.

Here are some things I would like you to know at this point or very soon.
  • What are polymers? How are monomers assembled into polymers? Explain hydrolysis and dehydration synthesis.
  • Identify the number of the carbons in a monosacharide both in linear and ring form.
  • What is the difference between an aldose and a ketose sugar?
  • What’s the difference between a triose sugar and a trisacharide? (or hexose versus hexasacharide).
  • How do sugars form the ring structure. Show that no atoms are gained or lost.
  • What is wrong with this sentence commonly found in biology texts “cells obtain energy by breaking the bonds in sugar molecules.” ? Students who had me in chemistry may have a leg-up on that one.
  • Explain the key differences and similarities between glycogen, starch and cellulose. What makes cellulose a good “structural” polysacharide? (you just read the answer).