BISC 330L Biochemistry Spring 2015 USC Lecture 5 Friday Jan 23 2015 Chapter 2 continues 2 2 Peptide bond and its geometry Formation of the Peptide Bond Most peptide bond formation requires energy Hydrolysis is extremely slow process kinetically stable Peptide has direction Peptide has backbone and sidechains Peptides can covalently linked by disulfide Cys disulfide can form intra inter chains Mass of a protein Polypeptide chains 50 20 000 amino acids Largest protein Titin 30K aa 3800kDa skeletal cardiac muscles Average size of amino acid 110 g mole 110 daltons Estimate molecular weight of protein N residue x 110 dalton protein of 100 residues MW 11kD Example Insulin Landmark in biochemistry because it showed that a protein is defined by its amino acid sequence Primary structure elucidate mechanism of action 3 D structure molecular patholgy Changes in the primary structure may lead to disease A slight change in the primary structure of a protein affects its ability to function The substitution of one amino acid for another in hemoglobin causes sickle cell disease a Normal red blood cell 2 3 1 4 5 Normal hemoglobin 7 146 1 2 3 4 5 7 146 b Sickled red blood cell Sickle cell hemoglobin 6 6 Mutations in FOXP3 cause severe autoimmune disease IPEX A B Stroud et al Structure 14 p159 2006 Peptide backbone geometry Double bond character resonance C N peptide 1 32 C N double bond 1 27 C N single bond 1 49 Consequence of resonance I planar structure of the peptide bond Consequence of resonance II Cis trans configuration of the peptide bond C C C C carbons on opposite sides Lower energy more favored carbons on same sides Higher energy less favored The case of Xaa Proline C C C C Cis and Trans forms have similar steric clashes Cis trans isomerization occurs in protein Cis Pro in nAChR Cys loop F P F D Cis Pro M e m b r a n e Rotation about single bonds in a polypeptide Horton R H Moran L A Ochs R Rawn J D and Scrimgeour K G 1996 Principles of Biochemistry 2nd ed Copyright Prentice Hall 1996 allows unique folding of proteins into many different 3 D structures Steric hindrance excludes many and combinations white Disfavored dark green most favorable light green allowed End of Lecture 5
View Full Document
Unlocking...