Amino Acids1/29/2003

Amino Acids:The building blocks of proteins

amino acids because of the carboxylic and amino groupspK1 and pK2 respectively pKR is for R group pK’s

pK1 2.2 while pK2 9.4

pK1pK2

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

AA1 AA2

20 x 20 = 400 different molecules

AA1 AA2 AA3

20 x 20 x 20 = 8000 different molecules

For 100 amino acid protein the # of possibilities are:

130100 1027.120 x

The total number of atoms in the universe is estimated at78109x

Characteristics of Amino AcidsCharacteristics of Amino AcidsThere are three main physical categories to describe amino acids:

1) Non polar “hydrophobic” nine in allGlycine, Alanine, Valine, Leucine, Isoleucine,

Methionine, Proline, Phenylalanine and Tryptophan

2) Uncharged polar, six in allSerine, Threonine, Asparagine, Glutamine Tyrosine,

Cysteine

3) Charged polar, five in allLysine, Arginine, Glutamic acid, Aspartic acid, and

Histidine

Amino Acids

You must know:

Their namesTheir structureTheir three letter codeTheir one letter code

H2N CH C

CH2

OH

O

OH

Tyrosine, Tyr, Y, aromatic, hydroxyl

Cystine consists of two disulfide-linked cysteine residues

Acid - Base properties of amino acids

[HA]

][Alog pK pH

-

ji pKpK2

1 pI

Isoelectric point: the pH where a protein carries no net electrical charge

For a mono amino-mono carboxylic

residue pKi = pK1 and pKj = pK2 ; for

D and E, pKi = pK1 and pKj - pKR ;

For R, H and K, pKi = KR and pKj =

pK2

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 2N possible stereoisomers and 2N-1 are enantiomericFor N = 2there are 4 possible sterioisomers of which 2 are enatiomersand 2 are diastereomers

Diastereomers are not mirror images and have different chemical properties.

StereoisomersStereoisomers

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

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>NH2>COOH>CHO>CH2OH>C6H5>CH3>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