Understanding the Importance of Amino Acid Structures in Protein Function, Study notes of Biochemistry

Download Understanding the Importance of Amino Acid Structures in Protein Function and more Study notes Biochemistry in PDF only on Docsity! Molecular Biology & Biochemistry 694:407 & 115:511 Structures of Amino Acids and Peptides Sept. 9th, 2005, Lecture Q: Why are the structures of amino acids important…? Proteins have a Language-Like Hierarchical Structure amino acids “alphabet” subdomain structures “words” folding units (domains) “sentences” • • • Etc. The Four Roles Played by Amino Acids in Proteins: • Structural • Activity • Spacing or linking • Gratuitous Proteins are polymers made up of amino acids subunits linked together in a particular sequence. The structures of the individual amino acids, and the sequence in which they occur, dictate the structure and properties of the protein. Nevertheless, it is hard to depict details of individual amino acid structures in the context of the rest of the protein -- sometimes there are just too many atoms! Thus, we often resort to schematic representations… Triose Phosphate Isomerase For example: Some generalizations: • There are 20 common amino acids that make up most proteins. • Amino acids in proteins are usually joined together via amide bonds termed “peptide” bonds. • Most amino acids are chiral molecules and contain a central carbon atom (C ) with tetrahedral geometry. Figure 4.1 Anatomy of an amino acid. Except for proline and its derivatives, all of the amino acids commonly found in proteins possess this type of structure. Amino Acids Building Blocks of Proteins Figure 4.6 The ionic forms of the amino acids, shown without consideration of any ionizations on the side chain. The cationic form is the low pH form, and the titration of the cationic species with base yields the zwitterion and finally the anionic form. 20 Common Amino Acids • Non-polar • Polar, uncharged • Acidic • Basic …BUT, this is an over-simplification. They all have different chemical “personalities”. Since nature is conservative, the genetic code gives clues to the chemical properties of many amino acids (i.e., what can easily mutate to what else? -- these often have similar side chains). Figure 4.3 The 20 amino acids that are the building blocks of most proteins can be classified as (a) nonpolar (hydrophobic), (b) polar, neutral, (c) acidic, or (d) basic. Also shown are the one-letter and three-letter codes used to denote amino acids. For each amino acid, the ball-and-stick (left) and space-filling (right) models show only the side chain. Figure 4.3 The 20 amino acids that are the building blocks of most proteins can be classified as (a) nonpolar (hydrophobic), (b) polar, neutral, (c) acidic, or (d) basic. Also shown are the one-letter and three-letter codes used to denote amino acids. For each amino acid, the ball-and-stick (left) and space-filling (right) models show only the side chain. Figure 4.3 The 20 amino acids that are the building blocks of most proteins can be classified as (a) nonpolar (hydrophobic), (b) polar,neutral, (c) acidic, or (d) basic. Also shown are the one-letter and three-letter codes used to denote amino acids. For each amino acid, the ball-and-stick (left) and space-filling (right) models show only the side chain. pKa Values of the Amino Acids • Arginine, Arg, R: pKa(guanidino group) = 12.5 • Aspartic Acid, Asp, D: pKa = 3.9 • Cysteine, Cys, C: pKa = 8.3 • Glutamic Acid, Glu, E: pKa = 4.3 • Histidine, His, H: pKa = 6.0 pKa Values of the Amino Acids • Lysine, Lys, K: pKa = 10.5 • Serine, Ser, S: pKa = 13 • Threonine, Thr, T: pKa = 13 • Tyrosine, Tyr, Y: pKa = 10.1 Since nature is conservative, the genetic code gives clues to the chemical properties of many amino acids (i.e., what can easily mutate to what else? -- these often have similar side chains). Figure 4.5 The structures of some amino acids that are not normally found in proteins but that perform other important biological functions. Epinephrine, histamine, and serotonin, although not amino acids, are derived from and closely related to amino acids. Green Fluorescent Protein Discovery: Prof. William Ward, Rutgers Univ. Use in living cells: Prof. Martin Chalfie, Columbia Univ. 3D structure Recombinant expression in vivo >>> adjacent Ser-Tyr-Gly residues + 3D structure forms a fluorophore! Figure 4.15 The ultraviolet absorption spectra of the aromatic amino acids at pH 6. (From Wetlaufer, D.B., 1962. Ultraviolet spectra of proteins and amino acids. Advances in Protein Chemistry 17:303–390.)