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10, 000 MIT June 2010 OEIT Star BioChem (LA and KMV) 1 10, 000 DNA lesions X 1 trillion cells 10,000,000,000,000,000 MIT June 2010 OEIT Star BioChem (LA and KMV) 2 DNA damage leads to mutations MIT June 2010 OEIT Star BioChem (LA and KMV) 3 DNA damage leads to mutations 1) toxic chemicals (industrial & environmental) 5) UV rays (sun) MIT June 2010 2) X-rays (clinic) 4) oxidation (respiration, smoking) 3) viruses (HPV) OEIT Star BioChem (LA and KMV) 4 DNA damage leads to mutations toxic chemicals (industrial & environmental) X-rays (clinic) mutations UV rays (sun) oxidation (respiration, radiation, smoking) MIT June 2010 disease viruses (HPV) OEIT Star BioChem (LA and KMV) 5 Oxidation can cause mutations in DNA MIT June 2010 OEIT Star BioChem (LA and KMV) 6 Oxidation can cause mutations in DNA MIT June 2010 OEIT Star BioChem (LA and KMV) 7 Oxidation can cause mutations in DNA MIT June 2010 OEIT Star BioChem (LA and KMV) 8 DNA glycosylase proteins help repair DNA damage caused by oxidation DNA glycosylases MIT June 2010 OEIT Star BioChem (LA and KMV) 9 Today’s activity: explore DNA glycosylases with Star BioChem (You can find it online too!) human hOGG1 (37 °C) MIT June 2010 archeabacteria Pa-AGOG (100 °C!) OEIT Star BioChem (LA and KMV) 10 Proteins perform many important biological functions hemoglobin carry oxygen in the blood MIT June 2010 F1 ATPase generate energy antibody protect against infections OEIT Star BioChem (LA and KMV) microtubules cell division aquaporin water transport 11 Protein Data Bank website The function of a protein is determined by its structure structure MIT June 2010 function OEIT Star BioChem (LA and KMV) 12 These two proteins both fix the same DNA defect. human hOGG1 archeabacteria Pa-AGOG Protein Evolution: 1) Proteins with similar functions tend to have similar 3D structures. 2) Proteins with similar 3D structures DO NOT ALWAYS have exactly the same amino acid sequence. The folding is important for function. MIT June 2010 OEIT Star BioChem (LA and KMV) 13 Amino Acids Identify the amino group, the acid group, and the side chains. The side chains are also called “R groups” (R = residues) Hydrophobic YELLOW (Polar) Hydrophilic GREEN Acid RED Base BLUE MIT June 2010 OEIT Star BioChem (LA and KMV) 14