Molecular Life Science Review

June 15, 2003 Learning objectives-

What is sickle cell anemia? Increased knowledge of the structure of atoms, molecules, and biomolecules Central Dogma How DNA mutations result in abnormal proteins Protein structure classifications How to perform comparisons of protein sequences

Workshops- Import cytochrome C sequences of different species. Perform Clustal W comparison Find out the molecular basis of sickle cell anemia

Symptoms of Sickle Cell Anemia

pain episodes strokes increased

infections leg ulcers bone damage yellow eyes or

jaundice early gallstones lung blockage

kidney damage and loss of body water in urine

painful erections in men (priapism)

blood blockage in the spleen or liver (sequestration)

eye damage low red blood cell

counts (anemia) delayed growth

Hierarchy of particles

Atoms (Eg. C, H, O, N)

Molecules (Eg. H2O, CH4)

small Biomolecules (Eg. Sugars, amino acids)

large Biomolecules (Eg. polysacharrides, proteins)

Example of ionic bond

H + H H2

O + O O2

2H2O 2H2 + O2

Chemical Reactions

Covalent Bonds(electrons shared)

pH scale. A convenient methodto measure the concentrationof H+

pH = -log[H+]

Remember pH + pOH = 14M = 1 mole/liter

Amino acid characteristics

Website for Amino acid interactive Workshop Amino acids

1 2

DNA sequenceWrite the primary sequence of the DNA displayed in 3Bhttp://www.blc.arizona.edu/Molecular_Graphics/DNA_Structure/DNA_Tutorial.HTML

http://www.rothamsted.bbsrc.ac.uk/notebook/courses/guide/dnast.htm

Website for interactive workshop for DNA analysis

Interactive display of amino acid and codons

Translation exercise

Translate the following sequence using the codontable:

ATGGUGCACCUGACUCCUGAGGAGAAG

Perform same procedure using a software program:

http://us.expasy.org/tools/dna.html

Central Dogma

DNA

RNA

Protein

DNA

RNA (with ribosomes)

*

>gi|1244762|gb|AAA98563.1| p53 tumor suppressor homolog

MSQGTSPNSQETFNLLWDSLEQVTANEYTQIHERGVGYEYHEAEPDQTSLEISAYRIAQPDPYGRSESYD

LLNPIINQIPAPMPIADTQNNPLVNHCPYEDMPVSSTPYSPHDHVQSPQPSVPSNIKYPGEYVFEMSFAQ

PSKETKSTTWTYSEKLDKLYVRMATTCPVRFKTARPPPSGCQIRAMPIYMKPEHVQEVVKRCPNHATAKE

HNEKHPAPLHIVRCEHKLAKYHEDKYSGRQSVLIPHEMPQAGSEWVVNLYQFMCLGSCVGGPNRRPIQLV

FTLEKDNQVLGRRAVEVRICACPGRDRKADEKASLVSKPPSPKKNGFPQRSLVLTNDITKITPKKRKIDD

ECFTLKVRGRENYEILCKLRDIMELAARIPEAERLLYKQERQAPIGRLTSLPSSSSNGSQDGSRSSTAFS

TSDSSQVNSSQNNTQMVNGQVPHEEETPVTKCEPTENTIAQWLTKLGLQAYIDNFQQKGLHNMFQLDEFT

LEDLQSMRIGTGHRNKIWKSLLDYRRLLSSGTESQALQHAASNASTLSVGSQNSYCPGFYEVTRYTYKHT

ISYL

FASTA format

Multiple sequence alignment Human-locus number AAA35732 Dog-locus number CCDG Yeast-locus number from structure

or protein sequence database 1YCC

CLUSTAL PROGRAM

Workshop Find out the chromosomal location of the gene

that causes sickle cell anemia. Give the name of the gene. Find out the nucleotide change and amino acid

change that leads to sickle cell anemia (there may be more than one change that gives rise to the disease)

If sickle cell anemia is so devastating, why has it lasted in the population for such a long time? Give a molecular explanation (you may have to do a little research to get this)

Print out answers and show instructor.