1. An overview of amino acid structure Topic 2

2. Biomacromolecule A naturally occurring substance of large molecular weight e.g. Protein, DNA, lipids etc. Proteins form the class of bio-macromolecule that have the most well- defined physicochemical properties and were generally easier to isolate and characterize than nucleic acids, polysaccharides or lipids. Proteins are essential to biochemical functions. The monomeric unit of protein is called the amino acids

3. Amino Acids Ball and stickspacefill  Proteins are linear polymers of amino acids connected by peptide bonds – amino acids are the building blocks of proteins  There are 20 standard amino acids. Asparagine was first found in 1806 and the last amino acid discovered (Threonine) was in 1938 (over 130 years later!!)  All 20 amino acids share common structural features:  -amino acids --each has a carboxyl group and an amino group bonded to the same  -carbon --differ in R group or side chain H R COO - C H3N+H3N+ Side-chain Amino group Carboxyl Group

4. Amino Acids

5. Amino Acid ionization

8. Amino Acids Alanine Arginine Asparagine Aspartic acid Cysteine Glutamic acid Glutamine Glycine Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Proline Serine Threonine Tryptophan Tyrosine Valine 3-Letter Ala Arg Asn Asp Cys Glu Gln Gly His Ile Leu Lys Met Phe Pro Ser Thr Trp Tyr Val 1-Letter A R N D C E Q G H I L K M F P S T W Y V Lehninger Principles of Biochemistry

9. Grouping of Amino Acids Some important terms:  Hydrophobic: tending to avoid an aqueous environment. Hydrophobic molecules are non-polar and uncharged. Amino acids with this property are usually buried within the hydrophobic core of the protein. Aliphatic: carbon atoms are joined together in straight or branched open chains rather than in rings. Aromatic: contains an aromatic ring system.  Hydrophilic: tending to interact with water. Hydrophilic molecules are polar and charged. Generally found on protein surface and exposed to aqueous environment.  Amphipathic: having both polar and nonpolar character. Classification of amino acids is “fuzzy”. There are several different grouping schemes.

10. Our classification hierarchy

11. It’s actually quite a bit more complicated…

12. Stereoisomers of Amino Acids  A "chiral" molecule cannot be superimposed with its mirror image  The amino acid residues in proteins are almost exclusively L-stereroisomers  D-amino acids are only found in a few small molecules  Glycine does not have a chiral center web99.arc.nasa.gov/~astrochm/

13. Nomenclature of Side Chain Atoms atomic symbol remoteness indicator branch designator Greek letters "A" for alpha, "B" for beta, "G" for gamma, "D" for delta, "E" for epsilon, "Z" for zeta, and "H" for eta. C, N, O, S 1, 2, 3…

14. Atom nomenclature within amino acids (as used within the PDB) CA CB C O N OG1CG2

15. Lys Arg To Do: Learn how to name the atoms of all amino acids. Hint: look at any generic PDB file to get a list of atom types. -The alpha carbon (CA) is immediately adjacent the most oxidized carbon (which is the CO 2 - in amino acids) -All the other heavy nuclei are named according to the Greek alphabet. -Put otherwise, LYS can be described by: CA, CB, CG, CD, CE, and NZ. Atom nomenclature within amino acids (as used within the PDB)

16. Numbers are used to discriminate between similar positions… CB CG OD1 ND2 CB CG ND1 CE1NE2 CD2 Here are some harder examples… CB CG CD2 CE2 CZ OH CD1 CE2 CB CG CD2 CD1 NE1 CE2 CH2 CE3 CZ2 CZ3 CB CD2 CD1 CG CB OG1CG2

17. ATOM 2518 CB ARG H 100 10.115 0.762 57.410 1.00 16.08 C ATOM 2519 CG ARG H 100 10.970 0.968 58.664 1.00 14.49 C ATOM 2520 CD ARG H 100 12.115 -0.023 58.757 1.00 17.17 C ATOM 2521 NE ARG H 100 12.888 0.203 59.977 1.00 16.50 N ATOM 2522 CZ ARG H 100 14.066 -0.354 60.234 1.00 17.58 C ATOM 2523 NH1 ARG H 100 14.620 -1.175 59.353 1.00 13.62 N ATOM 2524 NH2 ARG H 100 14.687 -0.088 61.380 1.00 17.77 N ATOM 2525 N TYR H 100A 7.182 2.284 55.730 1.00 12.75 N ATOM 2526 CA TYR H 100A 6.427 2.198 54.486 1.00 14.21 C ATOM 2527 C TYR H 100A 6.376 3.604 53.886 1.00 14.53 C ATOM 2528 O TYR H 100A 6.716 4.584 54.555 1.00 15.84 O ATOM 2529 CB TYR H 100A 5.008 1.657 54.732 1.00 14.11 C ATOM 2530 CG TYR H 100A 4.153 2.469 55.689 1.00 14.04 C ATOM 2531 CD1 TYR H 100A 3.708 3.754 55.357 1.00 14.99 C ATOM 2532 CD2 TYR H 100A 3.761 1.934 56.914 1.00 14.26 C ATOM 2533 CE1 TYR H 100A 2.890 4.480 56.224 1.00 14.63 C ATOM 2534 CE2 TYR H 100A 2.948 2.648 57.788 1.00 13.06 C ATOM 2535 CZ TYR H 100A 2.513 3.916 57.440 1.00 17.73 C ATOM 2536 OH TYR H 100A 1.690 4.600 58.311 1.00 16.51 O ATOM 2537 N PHE H 100B 5.974 3.698 52.623 1.00 14.33 N ATOM 2538 CA PHE H 100B 5.892 4.983 51.943 1.00 14.40 C ATOM 2539 C PHE H 100B 4.477 5.207 51.440 1.00 14.15 C ATOM 2540 O PHE H 100B 4.048 4.587 50.470 1.00 12.86 O ATOM 2541 CB PHE H 100B 6.908 5.020 50.798 1.00 15.51 C ATOM 2542 CG PHE H 100B 8.332 4.891 51.268 1.00 17.82 C ATOM 2543 CD1 PHE H 100B 8.834 3.656 51.668 1.00 17.78 C ATOM 2544 CD2 PHE H 100B 9.143 6.014 51.385 1.00 17.58 C ATOM 2545 CE1 PHE H 100B 10.126 3.538 52.185 1.00 17.48 C ATOM 2546 CE2 PHE H 100B 10.438 5.911 51.902 1.00 16.89 C ATOM 2547 CZ PHE H 100B 10.928 4.669 52.302 1.00 15.82 C ATOM 2548 N ASP H 101 3.762 6.107 52.113 1.00 16.17 N ATOM 2549 CA ASP H 101 2.369 6.394 51.790 1.00 17.29 C Nomenclature of Side Chain Atoms

18. Side-chain torsion angles

19. Side Chain Torsion Angles Number of  Amino Acid Types No  Only one  1  1,  2  1,  2,  3  1,  2,  3,  4  1,  2,  3,  4,  5 Gly, Ala Cys, Ser, Thr, Val Asn, Asp, His, Ile, Leu, Phe, Tyr, Trp Gln, Glu, Met Lys Arg Take this amino acid as an example

20. Side Chain Torsion Angles  It has been shown in the 70s by Janin et al. that different side-chain conformations do not have equal distribution over the dihedral angle space. Rather they tend to cluster at specific regions of the space. Janin J, Wodak S. “Conformation of amino acid side-chains in proteins”, J Mol Biol. 1978,125(3):357-86

21. Side Chain Torsion Angles Distribution of side-chain torsion angles for 6,638 leucine residues (403 crystal structures). The two major rotamers are labeled "1" and "2“. G.J. Kleywegt and T.A. Jones, Acta Cryst. D54, 1119-1131 (1998). Right image from Dunbrack’s lab

22. Side-chain torsion angles -With the exception of Ala and Gly, all sidechains also have torsion angles. -To Do on your own: -Count the # of chi’s in each amino acid. -Determine why Ala doesn’t have a chi angle.

23. Side Chain Rotamers  Rotamer: Rotational isomer  Rotamers are generally defined as low energy side-chain conformations.  Rotamers are knowledge-based. They are derived from statistical analysis of sidechain conformations in known protein structures through clustering observed conformations or by dividing torsion angle space into bins and determining an average conformation in each bin  Rotamer libraries: collections of rotamers for each residue type. In general, rotamer libraries contain information about both the conformation and the frequency of a certain conformation. There are several different types of rotamer libraies.

24. www.cryst.bbk.ac.uk Side Chain Torsion Angles  The different conformations of the sidechain as a function of χ1are referred to as gauche(+), trans and gauche(-).  The amino acid is viewed along the Cβ- Cα bond