Amino Acids 1/29/2003

Amino Acids: The building blocks of proteins  amino acids because of the  carboxylic and  amino groups pK 1 and pK 2 respectively pK R is for R group pK’s pK 1  2.2 while pK 2  9.4 pK 1 pK 2 In the physiological pH range, both carboxylic and amino groups are completely ionized

Amino acids are Ampholytes They can act as either an acid or a base They are Zwitterions or molecules that have both a positive and a negative charge Because of their ionic nature they have extremely high melting temperatures

Amino acids can form peptide bonds Amino acid residue peptide units dipeptides tripeptides oligopeptides polypeptides Proteins are molecules that consist of one or more polypeptide chains Peptides are linear polymers that range from 8 to 4000 amino acid residues There are twenty (20) different naturally occurring amino acids

Linear arrays of amino acids can make a huge number of molecules Consider a peptide with two amino acids AA1AA2 20 x 20 = 400 different molecules AA1AA2AA3 20 x 20 x 20 = 8000 different molecules For 100 amino acid protein the # of possibilities are: The total number of atoms in the universe is estimated at

Characteristics of Amino Acids There are three main physical categories to describe amino acids: 1) Non polar “hydrophobic” nine in all Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine, Proline, Phenylalanine and Tryptophan 2) Uncharged polar, six in all Serine, Threonine, Asparagine, Glutamine Tyrosine, Cysteine 3) Charged polar, five in all Lysine, Arginine, Glutamic acid, Aspartic acid, and Histidine

Amino Acids You must know: Their names Their structure Their three letter code Their one letter code Tyrosine, Tyr, Y, aromatic, hydroxyl

Cystine consists of two disulfide-linked cysteine residues

Acid - Base properties of amino acids Isoelectric point: the pH where a protein carries no net electrical charge For a mono amino-mono carboxylic residue pKi = pK 1 and pKj = pK 2 ; for D and E, pKi = pK 1 and pKj - pK R ; For R, H and K, pKi = K R and pKj = pK 2

The tetra peptide Ala-Tyr-Asp-Gly or AYDG Greek lettering used to identify atoms in lysine or glutamate

Optical activity - The ability to rotate plane - polarized light Asymmetric carbon atom Chirality - Not superimposable Mirror image - enantiomers (+) Dextrorotatory - right - clockwise (-) Levorotatory - left counterclockwise Na D Line passed through polarizing filters. } Operational definition only cannot predict absolute configurations

One or many chiral centers N chiral centers 2 N possible stereoisomers and 2 N-1 are enantiomeric For N = 2 there are 4 possible sterioisomers of which 2 are enatiomers and 2 are diastereomers Diastereomers are not mirror images and have different chemical properties. Stereoisomers

The Fischer Convention Absolute configuration about an asymmetric carbon related to glyceraldehyde (+) = D -Glyceraldehyde (-) = L -Glyceraldehyde

In the Fischer projection all bonds in the horizontal direction is coming out of the plane if the paper, while the vertical bonds project behind the plane of the paper All naturally occurring amino acids that make up proteins are in the L conformation The CORN method for L isomers: put the hydrogen towards you and read off CO R N clockwise around the C  This works for all amino acids.

An example of an amino acid with two asymmetric carbons

Cahn - Ingold - Prelog system Can give absolute configuration nomenclature to multiple chiral centers. Priority Atoms of higher atomic number bonded to a chiral center are ranked above those of lower atomic number with lowest priority away from you R highest to lowest = clockwise, S highest to lowest = counterclockwise SH>OH>NH 2 >COOH>CHO>CH 2 OH>C 6 H 5 >CH 3 >H

The major advantage of the CIP or RS system is that the chiralities of compounds with multiple asymmetric centers can be unambiguously described

Prochiral substituents are distinguishable Two chemically identical substituents to an otherwise chiral tetrahedral center are geometrically distinct.

Planar objects with no rotational symmetry also have prochariality Flat trigonal molecules such as aldehydes can be prochiral With the flat side facing the viewer if the priority is clockwise it is called the (a) re face (rectus) else it is the (b) si face (sinistrus).

Lecture 6 Monday Feb 3 Protein Geometry Primary sequence Sequence alignments