PowerPoint PresentationSlide 23-D Structure of MyoglobinImportance of ProteinsLevels of Protein StructureSlide 6Structure of -amino acidsThe 20 Amino Acids Found in ProteinsSlide 9Slide 10Stereochemistry of -amino acidsStereoisomers of -amino acidsProperties of Cysteine Side ChainSlide 14Absorption of UV Light by Aromatic Amino AcidsFormation of a PeptidePlanarity of Peptide (Amide) BondSlide 18cis and trans Isomers“Peptides”Examples of OligopeptidesSlide 22N- and C-Termini May Be Modified in ProteinsPrimary Structure of Bovine InsulinSlide 25Slide 26Evolution and Conservation of Protein SequencesSlide 28Molecular Biology & Biochemistry 694:407& 115:511Protein StructureSept. 13th, 2005, LectureSpecial thanks for this lecture goes to Dr. Gabriel Fenteany, Department of Chemistry, University of Illinois at Chicago (www.chem.uic.edu/fenteany/teaching/452), whose slides I liberally borrowed!3-D Structure of MyoglobinQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.Importance of Proteins•Main catalysts in biochemistry: enzymes (involved in virtually every biochemical reaction)•Structural components of cells (both inside and outside of cells in tissues)•Regulatory functions (if/when a cell divides, which genes are expressed, etc.)•Carrier and transport functions (ions, small molecules)Levels of Protein Structure•Primary Structure - amino acid sequence in a polypeptide•Secondary Structure - local spatial arrangement of a polypeptide’s backbone atoms without regard to side chain conformation (e. g., -helices and -sheets)•Tertiary Structure - three-dimensional structure of entire polypeptide•Quaternary Structure - spatial arrangement of subunits of proteins composed of multiple polypeptides (protein complexes)Structure of -amino acidsThe 20 Amino Acids Found in ProteinsStereochemistry of -amino acidsStereoisomers of -amino acidsAll amino acids are chiral except glycine.All amino acids in proteins are L-amino acids.Properties of Cysteine Side ChainSide chains with -SH or -OH can ionize, making them more nucleophilic.Oxidation between pair of cysteine side chains results in disulfide bond formation.oxidationreductionHCH3N+CH2COO-SHHCH3N+CH2COO-SSCH2CHH3N+COO-+ 2H++ 2e-CHH3N+CH2COO-SHCHH3N+CH2COO-SHH++pKa = 8.3CHH3N+CH2COO-S-Note: in cells, oxidative disulfide formation normally proceeds via a thiol-disulfide exchange reaction, with (for example) a natural tripeptide such as glutathione:R’-SH + R”-SH + G-SS-GR’-SH + R”-SS-G + G-SHR’-SS-G + R”-SH + G-SHR’-SS-R” + 2 G-SHG-SS-G = oxidated glutathioneG-SH = reducted glutathioneAbsorption of UV Light by Aromatic Amino AcidsFormation of a PeptidePlanarity of Peptide (Amide) BondQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.cis and trans IsomersQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.The trans isomer is generally more stable because of steric crowding of side chains in cis conformation.“Peptides”•Short polymers of amino acids•Each unit is called a residue•2 residues - “dipeptide”•3 residues - “tripeptide”•12-20 residues - “oligopeptide”•Many residues - “polypeptide”Examples of OligopeptidesN- and C-Termini May Be Modified in ProteinsPrimary Structure of Bovine InsulinFirst protein to be fully sequenced;Fred Sanger, 1953. For this, he won his first Nobel Prize (his second was for the Sanger dideoxy method of DNA sequencing).Evolution and Conservation of Protein SequencesAlmost all human genetic diseases involve the disruption of a protein in the body. Typically, the harmful phenotype(s) of disease-causing lesions in a protein gene are caused by effects on (a) the level of expression of the protein, (b) the activity of the protein, or (c) the folding of the protein. [Note: Some effects may be different in different tissues for the same mutation! For example, some alpha-1-antitrypsin mutations exert harmful effects in the lungs (emphysema) due to lack of anti-elastase activity, and different harmful effects in the liver (cirrhosis) due to folding/sorting