1. 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

2. 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

5. Hierarchy of particles Atoms (Eg. C, H, O, N) Molecules (Eg. H 2 O, CH 4 ) small Biomolecules (Eg. Sugars, amino acids) large Biomolecules (Eg. polysacharrides, proteins)

7. Example of ionic bond

8. H + H  H 2 O + O  O 2 2H 2 O  2H 2 + O 2 Chemical Reactions

9. Covalent Bonds (electrons shared)

13. pH scale. A convenient method to measure the concentration of H + pH = -log[H + ] Remember pH + pOH = 14 M = 1 mole/liter

19. Amino acid characteristics

20. Website for Amino acid interactive Workshop Amino acids 1 2

24. DNA sequence Write the primary sequence of the DNA displayed in 3B http://www.blc.arizona.edu/ Molecular_Graphics/DNA_Str ucture/DNA_Tutorial.HTML http://www.blc.arizona.edu/ Molecular_Graphics/DNA_Str ucture/DNA_Tutorial.HTML http://www.rothamsted.bbs rc.ac.uk/notebook/courses/g uide/dnast.htm http://www.rothamsted.bbs rc.ac.uk/notebook/courses/g uide/dnast.htm Website for interactive workshop for DNA analysis

25. Interactive display of amino acid and codons

26. Translation exercise Translate the following sequence using the codon table: ATGGUGCACCUGACUCCUGAGGAGAAG Perform same procedure using a software program: http://us.expasy.org/tools/dna.html

27. Central Dogma DNA RNA Protein

28. DNA RNA (with ribosomes)

29. *

31. >gi|1244762|gb|AAA98563.1| p53 tumor suppressor homolog MSQGTSPNSQETFNLLWDSLEQVTANEYTQIHERGVGYEYHEAEPDQTSLEISAYRIAQPDPYGRSESYD LLNPIINQIPAPMPIADTQNNPLVNHCPYEDMPVSSTPYSPHDHVQSPQPSVPSNIKYPGEYVFEMSFAQ PSKETKSTTWTYSEKLDKLYVRMATTCPVRFKTARPPPSGCQIRAMPIYMKPEHVQEVVKRCPNHATAKE HNEKHPAPLHIVRCEHKLAKYHEDKYSGRQSVLIPHEMPQAGSEWVVNLYQFMCLGSCVGGPNRRPIQLV FTLEKDNQVLGRRAVEVRICACPGRDRKADEKASLVSKPPSPKKNGFPQRSLVLTNDITKITPKKRKIDD ECFTLKVRGRENYEILCKLRDIMELAARIPEAERLLYKQERQAPIGRLTSLPSSSSNGSQDGSRSSTAFS TSDSSQVNSSQNNTQMVNGQVPHEEETPVTKCEPTENTIAQWLTKLGLQAYIDNFQQKGLHNMFQLDEFT LEDLQSMRIGTGHRNKIWKSLLDYRRLLSSGTESQALQHAASNASTLSVGSQNSYCPGFYEVTRYTYKHT ISYL FASTA format

32. Multiple sequence alignment Human-locus number AAA35732 Dog-locus number CCDG Yeast-locus number from structure or protein sequence database 1YCC CLUSTAL PROGRAM

33. 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.