Peptide Bonds & Protein Structure: Amino Acids, Torsion Angles & Interactions, Study notes of Biochemistry

Download Peptide Bonds & Protein Structure: Amino Acids, Torsion Angles & Interactions and more Study notes Biochemistry in PDF only on Docsity! 1 Reading assignments: L (2) p75-80 L (3) p47-55, 88-89 What amino acids really look like Tetrahedral carbon Cα Page 13 Molecular Asymmetry Page 18 Carbon with 4 different substituent groups (hand) 2 Looking along the H-Cα bond with H atom closest to you Reading clockwise, the groups attached to the Cα spell CORN Amino acid Structure The central carbon (Cα-atom) is a chiral center Encoded proteins have the L-configuration at this chiral center Configuration can be remembered as the CORN law When an amino acid is incorporated into a polypeptide by the ribosome at position i in the sequence, it undergoes a condensation reaction in which the carboxyl group of the preceding amino acid (i-1) forms an amide (or peptide) bond with the amino group residue i. In the next elongation cycle of the ribosome, the carboxyl group of residue i becomes covalently linked to the amino group of residue i+1 in the final sequence by another peptide bond Peptide Bond All amino acids have amino and carboxyl groups The Polypeptide chain Amino acids in proteins (or polypeptides) are joined together by peptide bonds and have different properties: acidic, basic, neutral, hydrophobic, etc (see L2) The amino acid side-chains also direct the folding of the nascent polypeptide and stabilize its final conformation Amino terminus NH2 Carboxyl terminus HOOC Polypeptide chain Page 119 5 Protein Folding Concept of protein folding energy well Many weak interactions Only 10 KJmol-1 differentiates a folded functional to a precipitated protein 6 Noncovalent Interactions between amino acids (in a folded protein) Hydrogen bond -CH2-OH ………O-C- (~4.0-40.0 KJmol-1) H donor/acceptor Hydrophobic interactions displacement of water (~0.4-4.0 KJmol-1) Π bonding aromatic amino acid stacking (~0.4-4.0 KJmol-1) Van der Waals interactions weak (but many) (~0.4-4.0 KJmol-1) Electrostatic pH effect/repulsion (~4.0-40.0 KJmol-1) Salt bridge Asp, Glu (carboxyl side chain) (~40.0-400.0 KJmol-1) Arg, Lys (basic side chain) Hydrogen bond Polar amino acids Noncovalent Forces— Hydrogen Bonds R-NeH--O=C-R * Largely due to ionic interactions. (Think of H-bond as a proton-sharing acid-base interaction.) * The strongest hydrogen bonds share three features: * Possess favorable proton-donor/acceptor properties. * The N--H--0 atoms are arranged linearly. * They have 2.9-3.3 A N-to-O bond-lengths. \g force for protein folding, because 2 H-bonds are made and 2 H-bonds are broken: R-N---H---OH, + HOH--O=C-R However, formation of extended H-bond networks (especially those in a-helix or B-sheets) partially compensate for loss of R-N~-H~-OH, and HOH~-O=C-R H-bonds. Noncovalent Forces— Hydrophobic Interactions + Strictly speaking, these stabilizing interactions are NOT true bonds (No overlapping of atomic or molecular orbitals) * Because no orbital overlap occurs in hydrophobic interactions, the strength of intaraction is unaffected by geometric considerations * The great variety of hydrophobic side-chains maximizes protein's interior density and maximizes release of bound water. Ala Vall Leul CH te Ce wc So, dy da nec ow’, » OF Mel Trp] Tyr! HE—CH, CH Cte Noncovalent Forces— 1-Cation Interactions H oe same as ( ‘} oy mee oH vmonviaianne —qythne Tryptophan mer YOR ‘Tips - Bond is fairly strong and geometrically well directed. + Amino acids involved in 7-cation Interactions: : Phenylalanine, Tyrosine, Tryptophan & Histidine” jeutral tor) Noncovalent Forces— van der Waals interactions + Interactions that operate over short distances Attractive force « (Distance)* + Resulting from the overlap of shortlived, highly fluctuating dipoles of so-called non-bonding electron orbitals. When time-averaged, the net effect is a relatively weak bond. + Within the densely packed protein interior, numerous van der Waals interactions sum up and contribute considerable stability to a well folded protein Again, the availability of hydrophobic groups of many sizes and shapes facilitates dense packing. + Helps explain why seemingly conservative substitutions of one hydrophobic side-chain by another hydrophobic side-chain can greatly alter protein stability