Protein Structure: Primary & Secondary Structure Lecture 3 PDF

Protein Structure: Primary Structure and Secondary Structure Lecture 3 BCMB 401 Spring 24 Reading: Chapter 2.2-4 AMINO ACID STRUCTURE AND PROPERTIES amino group α-carbon carboxyl group Consists of a central α-carbon with attached amino (pKa ~9-10) group, carboxyl (pKa ~2) group and a hydrogen atom....

Protein Structure: Primary Structure and Secondary Structure Lecture 3 BCMB 401 Spring 24 Reading: Chapter 2.2-4 AMINO ACID STRUCTURE AND PROPERTIES amino group α-carbon carboxyl group Consists of a central α-carbon with attached amino (pKa ~9-10) group, carboxyl (pKa ~2) group and a hydrogen atom. R-group (side chain) is variable and defines the chemical and structural properties of amino acids Two possible stereoisomers - all naturally occurring protein amino acids are in L-configuration. In R-, S- system: most L amino acids are in Sconfiguration, exception is cysteine 20 different amino acids in polypeptides you need to know them all AMINO ACIDS polar, uncharged nonpolar negative positive Proteins: 1 to 4 Structure Primary Secondary Tertiary Quaternary Primary structure: sequence of covalently bonded amino acids PRIMARY STRUCTURE: The Peptide Bond Amide bond between the α-carboxylate of one amino acid and the α-amino group of another Amino acids in a peptide are referred to as amino acid residues Charges on NH3+ and COO- groups forming the peptide bond are lost Extremely hydrophilic with high tendency to form hydrogen bonds Kinetically stable - very slow rate of breakdown (years) PRIMARY STRUCTURE: The Peptide Bond Nomenclature: This is a pentapeptide with the sequence: tyr-gly-gly-phe-leu (three letter code) YGGFL (single letter code) There is a polarity to peptides with the free positively (+) charged amino terminus on one end and the free negatively (–) charged carboxyl terminus on the other end The polypeptide consists of a repeating part called the main chain or backbone and a variable part consisting of the distinctive amino acid side chains. The properties of the peptide are determined by the free R-groups which contribute to the charge and hydrophobicity of the peptide structure Biological peptides can be small but generally polypeptide chains are 50-2000 amino acid residues in length The Peptide Bond Because of resonance stabilization, the peptide bond has partial double bond character This results in no free rotation about this C—N bond The peptide bond is essentially planar. Six atoms (Cα, C, O, N, H, and Cα) lie in a plane. This is a critical property for consideration of higher order protein structure The Peptide Bond Because of steric clashes, virtually all peptide bonds in proteins are in the trans configuration with the two α-carbon atoms on opposite sides of the peptide bond. The exception is proline, which can be found in either orientation when proline follows another amino acid in a peptide bond (X-Pro) Proline Polypeptide chains are flexible, yet conformationally restricted φ ψ φ ψ Rotation is permitted about the N-Cα bond [the phi (φ) bond] and about the Cα-carbonyl bond [the psi (ψ) bond]. The rotation about the φ and ψ bonds, called the dihedral (torsion) angle, determines the path of the polypeptide chain. The Peptide Conformation and Ramachandran Plot Ramachandran plot: illustrates the φ and ψ angle combinations that are allowed (light green) and favorable (dark green) Three-quarters of the possible (φ, ψ) combinations are excluded by local steric clashes. Ramachandran plots similar for 18 of the 20 amino acids. Two amino acids have unique Ramachandran plots: glycine and proline Glycine Proline Rotations about N-Cα (φ) and Cα-C (ψ) only for the alanine residue at the center in a pentapeptide (the motions of the other residues are frozen). On the right, the corresponding changes of φ and ψ values in Ramachandran plot are given for the central alanine residue. Peptide bonds (in red circles) remain planar Ramachandran plot N-Cα bond and Cα-C single bonds. The rotations about these bonds lead to the changes of φ and ψ, respectively. PROTEINS: 1 to 4 Structure Primary Secondary Tertiary Quaternary Secondary Structure – local structural elements stabilized by backbone amide to carbonyl oxygen hydrogen bonding α helix, β sheet, turns SECONDARY STRUCTURE: The  helix α helix = tightly coiled, rod-like structure, with the R groups extending outward Very compact.: 1.5 Å linear distance per residue (5.4 Å per turn / 3.6 amino acid residues per turn) All of the backbone CO and NH groups form hydrogen bonds except those near the ends of the α helix. The CO group (acceptor) of each amino acid forms a hydrogen bond with the NH group (donor) of the amino acid that is situated four residues ahead in the sequence. i to i+4 pattern where i is CO and i+4 is NH SECONDARY STRUCTURE: The  helix Essentially all α helices found in proteins are right-handed. Glycine and proline rarely found in α helices Glycine – entropically unfavorable to constrain in an α helix Proline – lacks an NH group to serve as hydrogen bond donor, and its ring structure prevents it from assuming the φ value to fit into an α helix. SECONDARY STRUCTURE: The -Strand Fully extended structure; 3.5 Å between adjacent residues Side chains of adjacent amino acids point in opposite directions Better accommodate bulkier amino acid side chains SECONDARY STRUCTURE: The -Sheet Antiparallel -Sheet Parallel -Sheet Stabilized by inter-strand amide N to carbonyl O hydrogen bonds Stabilized by inter-strand amide N to carbonyl O hydrogen bonds The NH and CO groups of one amino acid on one strand make hydrogen bonds to CO and NH groups of one other amino acid on adjacent strand The NH and CO groups of one amino acid make hydrogen bonds to the CO of one amino acid and the NH group of a different amino acid two residues down the adjacent strand SECONDARY STRUCTURE: -Sheet Mixed β sheets contain strands parallel and anti-parallel to one another Stabilized by inter-strand hydrogen bonds β-sheets consist of multiple βstrands Ribbon diagram – arrow pointing in direction of C-terminus SECONDARY STRUCTURE: Turns OTHER STRUCTURAL ELEMENTS: Loops Amino Acids most commonly found in turns and loops include: Glycine Proline Small, polar and uncharged (Asn, Ser) Small charged (Asp) Turns: 5 or fewer residues and must have a hydrogen bond Loops: 6 or more residues OR 5 or fewer with no hydrogen bond Reverse Turn (β turn) Often stabilized by i to i+3 (CO to NH) hydrogen bond Abrupt (tight) change in direction of polypeptide chain Loops (Ω loops) Can be structured or unstructured (floppy) Sometimes have a functional role Visualizing Molecular Structures: Proteins Ribbon Sticks Spheres