Chapter 9Proteins

Amino AcidsProtein StructureProtein Functions Enzymes—Life’s Catalysts

Amino Acids

H O | || H2N – C – C – OH

| R

amino group carboxyl group

side chain

There are 20 different (genetically encoded) amino acids.These differ only in the nature of the side chain, R.

a carbon

Amino Acids

H O | || H2N – C – C – OH

| R

The amino group is a base and can accept a proton.

The carboxylic acid group is an acid and can donate a proton

H O | || ↔ H2N – C – C – O-

| R + H+

H O | || H3N+ – C – C – OH ↔

| R

+ H+

1. Given that ‘R’ for the amino acid alanine is –CH3, Draw the structure of alanine. Given that the pK’s are 2.3 for the -COOH group and 9.7 for the –NH2 group, describe it’s ionic form at various pH values. What is it’s ionic form in blood at pH 7.4?

pH Acid form Base form= pK equal equal< pKa more less

> pKa less more

pK = 2.3pK = 9.7

Amino Acid at ~ pH 7

H O | || H3N+ – C – C – O-

| R

Except for Glycine ( R = H) all amino acids have a chiral C.

However only the ‘L’ form exists in nature.

Natural Carbohydrate molecules (e.g. sugars) are ….

a) always D b) always L c) either d) not chiral

Amino acids are typically classified based on the structure of the side chains as ……

Nonpolar C and H atoms only (also Methionine – a thioether)

Polar O and N in forms that cannot form ions (ionize)alcohols, amides

acid form conjugate base

Acidic COOH – carboxyl group - COOH ↔ -COO- + H+

base form conjugate acid

Basic amino group (-NH2) H+ + NH2 ↔ NH3+

could be 2ndary amine but not amide

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Nonpolar amino acids

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Nonpolar amino acids

Could be considered polar or nonpolar

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Polar amino acids

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Acidic amino acids

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Basic amino acids

Combination of amino acids by a condensation reaction

Combination of amino acids by a condensation reaction

Dipeptide

Tripeptides − oligo peptides − polypeptides

A biologically active polypeptide containing 50 or more amino acids is a protein.Proteins may also contain more than one polypeptide chain (subunits).They must fold up into a specific, functional structure.

Aspartame, an artificial sweetener, is a modified dipeptide (at pH 7.4)

H O | ||H3N+ – C – C –

| CH2

| COO-

H O | || - N – C – C – O – CH3

H | CH2

|

Protein Structure

Primary StructureThe primary (1) structure of a protein is the order in which the amino acids are joined together to form the protein backbone.

The side chains of the amino acids are substituents dangling from this backbone.

The peptide bond is the covalent bond that forms this level of protein structure.

Note that the backbone repeats …..

amino endcarboxy end

The amino and carboxy ends are typically charged at pH 7.4

Protein Structure: Secondary StructureBackbone hydrogen bonding

C = O ••• H – N Hydrogen bonding

a-helixCoiled structure

Like spring

b-sheetextended structure

zig-zag due to 109º

or 120º

Protein Structure: Tertiary StructureSide chain interactions

disulfide bonds covalent – 2 Cys only

H-bonds 2 polar side chains

Salt bridge 1 acidic + 1 basic side chainboth need to be ionized (like ionic bond)

Hydrophobic Nonpolar side chains Interactions inside of protein away from water (solvent)

Protein Folding

External side chains (polar/acidic/basic) can interact with water rather than another amino acid

Protein Folding

Proteins are a cell’s tool kit.They each have a job to do (function) …… and a shape that is specific to the job they must perform.

Proteins are a cell’s tool kit.They each have a job to do (function) …… and a shape that is specific to the job they must perform.

Globular vs. Fibrous Proteins• Globular proteins fold into a compact, spherical shape with polar amino

acid side chains on their surface and nonpolar amino acid side chains forming a nonpolar core. Enzymes and many cellular proteins are globular proteins.

• Fibrous proteins have long, thread-like structures. Fibrous proteins tend to be insoluble in water. e.g. wool, silk, & collagen

(skin, bone, tendons, & ligaments)

Protein Folding

Globular

Fibrous

TripleHelix

Collagen

2

CH2

CH

CH2

Proline (Pro)

ProlineHydroxylase

N Ca CO

Proline is ….. a) nonpolar b) polar c) acidic d) basic

Hydroxyproline is ….. a) nonpolar b) polar c) acidic d) basic

Hydroxyproline (Hyp)

OH

CH2

- CH2 - CH - OHHO - CH - CH2

| CH2

H-bonds cross-linkcollagen chains

Scurvey : Disease associatedwith Vitamin C deficiency

...caused by weakness in connective tissue

... caused by failure to form sufficient cross-links in collagen

... caused by insufficent vitamin C for Proline Hydroxylase (Fe3+) reduction

Should you make sure your pet dog gets enough vitamin C? a) yes b) no

Vitamin C is synthesized metabolically in all animals except …. humans, bats, guinea pigs, monkeys/apes (some fish/birds?)

Osteogenesis Imperfecta

Cause: mutation in gene for procollagen a-1 chain

Effect: interfere with 3-helix formation - collagen used to make bone is weaker

Procollagen a-1 chain: mutationsGly221 Cys OI mild form Gly389 Cys OI moderate form

Gly425 Ser OI lethal form

Disease of? A) muscle b) nerves c) blood d) bones

Soluble Collagen Disease

SColD

Protein Folding

Proteins are a cell’s tool kit.They each have a job to do (function) …… and a shape that is specific to the job they must perform.

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Messengers, Receptors, and Transporters• A hormone is a chemical, sometimes a peptide or protein, created

in one part of the body that affects another part of the body.• Receptors are proteins facing the outer surface of a cell that bind

to a hormone or other messenger, triggering a signal inside the cell.• A transporter is an integral membrane protein spanning a

phospholipid bilayer.

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Antibodies• The substance recognized by an antibody is called an antigen. (typically a protein) e.g. virus – bacteria – venom - undigested food protein (nuts – shellfish – etc.) • The quaternary structure is held together through disulfide bridges between the

polypeptide chains.• The stem of the Y is similar in all antibodies. Antibodies bind antigens at the top of

each arm of the Y.

Insert figure 10.10, page 402

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Hemoglobin• Hemoglobin has 4 subunits 4 polypeptide chains = a2b2

• Each subunit contains a heme prosthetic group.• Each heme group binds Fe2+, which, in turn,

binds oxygen (O2). • Each Fe2+ can bind one oxygen molecule:

one hemoglobin can transport four moleculesof oxygen.

H+Hb (deoxy Hb) + 4O2 ↔ Hb(O2)4 + H+

deoxyHb and Hb have different structures. The amount of O2 helps to regulate the structure and oxygen binding.

Hb structure is designed to bind O2 in the lungs ….. … and release it in capilaries

Myoglobin, Mb picks up O2 in the cells ….. … and release it in the Mitochondria where it is used to ATP production (Oxidative Phosphorylation)

PO2 in lungs

PO2 in ‘cell’

mito

mito

mito

mito

Hb

Mb

Tissue cell

blood

Hb structure is designed to bind O2 in the lungs ….. … and release it in capilaries

Myoglobin, Mb picks up O2 in the cells ….. … and release it in the Mitochondria where it is used to ATP production (Oxidative Phosphorylation)

PO2 in lungs

PO2 in ‘cell’