INTRODUCTION3. Protein Structure Background
4. Normal and Mutant Hemoglobin Structure Interactive
Start here:INTERNET SEARCH
We will search using a standard Internet search engine called Google.
First search with the phrase:
sickle cell anemia
hint: you can copy and paste for less typing
Scan the hits to see the nature of the sites found by your search. Scroll down to the hit TUTORIAL: Sickle-cell Anemia enter this site and scan. Go to links section and enter the site:
www.wadsworth.org/chemheme/heme/microscope/sicklecellanemia.htm
here you can view micrographs (microscope-photos) of several kinds of affected red blood cells
Another Search
Now we will google search with another search phrase:
click here Google
and type or paste
mendelian inheritance
Click on the top hit
OMIM -Online Mendelian Inheritance in Man
can't find it? Click here
Now from here click on
Search the OMIM Database
enter
sickle cell anemia
You will see a list of hits to this query
click on the entry labeled 603903, Sickle Cell Anemia
now click on Edit History
this will indicate how lately the database has been updated
it's always good to know how "old" the information is...
click Back
click on the link 141900 found several sentences down in Text
This is a huge file with a lot of scientific/medical information
when was this entry last updated?
after scanning the content click (at the top)
on View List of allelic variants
remember an allele is any type of coding variation occurring at a particular gene locus (physical location)
scroll down for the entry
.0243 HEMOGLOBIN S
Read some of this entry, which describes the most common allelic variation of the Hemoglobin gene leading to sickle cell anemia
you may also notice that this allele is described as a glutamic acid to valine mutation in the hemoglobin beta locus
Lets explore what this is all about
But first we need some
Protein Background!!
Click here for a short tutorial
click DNA Replication
this is a simplified cartoon of a gene being replicated, with the gene sequence shown beside
go back
then click Protein Synthesis
this is a simplified cartoon of a protein being made from a gene
the protein is the small string of balls, each ball is an amino acid
go back
here is a protein sequence entry at a national database
Each letter represents one of 20 common amino acids
the red E represents glutamic acid 6, which is changed to valine in the mutant hemoglobin S, which leads to Sickle Cell Anemia
go back
click on amino acids to learn what they are
How they are connected to make protein
go back and then click fold
this is a simplified picture of a folded protein, drawn as a dot-to dot from the center of each of the 76 amino acids
go back
proteins can contact each other, for chemical reactions and scaffolding and other biological functions
click on complex
this shows 3 views of the same 2 proteins bound together
now onto an interesting interactive structure experience from UMass-Amherst
click here for fastest version (here is a slower web-version from UMass-Amherst)
if you don't have Chime download it here
Click on Hemoglobin
this starts a tutorial on normal and sickle cell Hemoglobin protein structure
start by clicking Hemoglobin & Heme
click on the first "X in the box" in the right frame
the protein is shown as beads on a string instead of a smooth line as before
work through all of these in Hemoglobin & Heme
then SKIP
Hemoglobin Secondary Structure Alpha Helix Amphipathicity Hydrophobicity, Polarity, & Charge
and go onto Sickle Hemoglobin and work through this one
To see a great picture of the polymerized Hemoglobin S in the crystal lattice
and the Glu-to-Val mutation in real space!
These figures are from:
The High Resolution Crystal Structure of Deoxyhemoglobin S
Daniel J. Harrington, Kazuhiko Adachi, William E. Royer, Jr
The Journal of Molecular Biology
V272 No. 3 pp. 398-407 September 1997
click here for a short e-movie on these fibers
click the Sickle Cell Hemoglobin picture
scroll down the right frame to
Super Tour with Full-Length Movie (Fastest Connections)
