On a FREE AMINO ACID, what functional groups will accept or donate protons at pH 7, and hence are normally charged in water?

side chain groups

-OH

-CH3

-C O

-NH2

-COOH

the group “COOH” would be a very strong acid

in fact, this group is always deprotonated, and thus exists as a weak base, COO-

AA’s are zwitterions at pH 7, because they have oppositely charged groups

amino acids are salts with high melting points, because as they crystallize, ionic interactions stabilize the crystal lattice

Titration curve for alanine

pK1 = 2.4 pK2 = 9.9 pIAla = isoelectric point

pKa values of

amino acid ionizable

groups

Which amino acid side chains are positively charged at pH 7?

Which amino acid side chains are negatively charged at pH 7?

Which amino acid side chains can act as H-bond donors?

Which amino acid side chains can act as H-bond acceptors?

Aliphatic side chains

Aromatic side chains

Proline has a nitrogen in an aliphatic ring system

• Proline (Pro, P) - has a three carbon side chain bonded to the -amino nitrogen

• The heterocyclic pyrrolidine ring restricts the geometry of polypeptides

Methionine and cysteine

Cys can participate in S-S bonds that covalently link different parts of a polypeptide chain to stabilize the 3D structure of a protein

Side Chains with Alcohol Groups

- can donate & accept H-bonds, but are NOT charged!

- can be phosphorylated by kinase enzymes

Acidic or polar side chains

Basic amino acids

Due to resonance, all lone pairs are partially occupied by the proton in its normal, positively charged state

Side chain of arginine

Peptide bond between two amino acids

Peptide bond shown as a C-N single bond

Peptide bond shown as a double bond

Actual structure is a hybrid of the two resonance forms w/ delocalized electrons

Planar peptide groups in a protein

• Rotation around C-N bond is restricted due to 40% double-bond nature of the resonance hybrid form

• Peptide groups (blue planes) are therefore planar; restrict conformations possible in protein chains

features of the peptide backbone

What parts of this polypeptide are charged at pH 7 ?

What groups can accept H-bonds?

What groups can donate H-bonds?

[ Hint: what is different for a peptide versus a free amino acid? ]

draw your amino acids as part of a peptide backbone, not as free aa’s, on your homework and quizzes!!

Both backbone and side chain groups participate in important intra- and inter-molecular binding interactions

- some are responsible for folding protein into correct 2D and 3D shape

- others bind to small molecules like enzyme cofactors & substrates

Features of protein secondary structure (commonly encountered folding patterns) like b-sheets are due to repeated H-bonding between backbone groups of a protein