19-1

Principles and Applications ofInorganic, Organic, and

Biological ChemistryDenniston, Topping, and Caret

4th ed

Chapter 19

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Power Point to Accompany

19-2

IntroductionProteins:

Provide nitrogen and sulfur for the diet

Most abundant macromolecules in the cell

Carry out most of the work of the cell

19-3

19.1 Cellular Function of Proteins• Are biological catalysts (enzymes)• Are antibodies that fight antigens

(bacteria and viruses)• Transport molecules and ions• Regulate cell function• Provide structural support and

mechanical strength• Are necessary for all forms of

movement• Are sources of amino acids for growth

19-4

Four Levels of Protein Structure

Primary, 1o

the amino acid sequenceSecondary, 2o

3-D arrangement of backbone atoms in space

Tertiary, 3o

3-D arrangement of all the atoms in space

Quaternary, 4o

3-D arrangement of subunit chains

19-5

19.2 The -Amino AcidsAn alpha amino acid is a carboxylic acid

with an amino group on the carbon alpha to the carboxylic acid .

The alpha carbon also has an R group side chain except for glycine which has two Hs.

C C

R1

H

NH3

+O

OGeneric aminoacid at physiologicalpH. C

19-6

If the R group is not H, the AA can exist in two enantiomeric forms (nonsuperimposable mirror image) forms.)

Mirror plane carbon

C

C

R1

HNH3

+

OO

C

C

R1

H NH3

+

O O

Amino acids incorporated into proteins have the L- configuration.

19-7

AA with nonpolar side chains-1

C COO-

CH3

HNH3

+

alanine, alaCH2

C COO-

HNH3

+

phenylalanine,Phe

C COO-

CH2

HNH3

+

CHCH3

CH3

leucine,leu

C COO-

CH

HNH3

+

CH2CH3

CH3

isoleucine, Ile

19-8

AA with nonpolar side chains-2

C COO-

CH

HNH3

+

CH3 CH3CH2

C COO-

HNH3

+

CH2S CH3

C COO-

CH2

HNH2

+

CH2

CH2

valine, val methionine, Met

proline, Pro

C COO-

CH2

HNH3

+

CCHN

Htryptophan, Trp

19-9

AA with polar side chains-1

C COO-

H

HNH3

+

CH2

C COO-

HNH3

+

OH

C COO-

CH2

HNH3

+

SH

glycine, gly serine, ser

cysteine, cys

C COO-

CH

HNH3

+

CH3

OH

threonine, thr

19-10

AA with polar side chains-2

glutamine, Gln

tyrosine, Tyr

C NH2O

CC

HNH3

+OO

CH2

C NH2O

CH2

CC

HNH3

+OO

CH2

asparagine, Asn

OHCC

CH2

HNH3

+OO

19-11

AA: acidic and basic

glutamic acid, GluC OO

CCOO

-

HNH3

+

CH2

C OO

CH2

CCOO

-

HNH3

+

CH2

aspartic acid, Asp

CH2NH

CH2CH2

CNH2

+NH2

CCOO

-

HNH3

+

CH2CH2

CH2

CCOO

-

HNH3

+

CH2

NH3

+

NHCH

CH2

CCOO

-

HNH3

+

CNH

+CH

histidine, Hislysine, Lysarginine, Arg

19-12

19.3 The Peptide BondA peptide is a polymer of about 2-100 amino acids linked by the peptide(amide) bond. As the amino group and the carboxyl group link, water is lost.

C C

R1

H

NH3

+O

OC C

R1

H

NH3

+O

OC C

R1

H

NH3

+O

O

C C

R1

H

NH3

+O

C C

R1

H

NH

OC C

R1

H

NH

OO

Peptide bonds

-H2O -H2O

19-13

Peptide Bond, Cont.There is restricted rotation about the

peptide bond due to resonance. This restricted rotation has important consequences in terms of protein structures.

R

NH3

+

CHCO

NH

C R

NH3

+

CHCO

NH

C

+

-

19-14

Peptides: Structure and NamesStructure left (N-term) to right (C-term)

Structure is based on the repeating sequence

N-C-C-N-C-C-N-C-C

N is the -amino group; white is the a-carbon; and yellow is the carbonyl carbon.

Name peptides by prefixing (L to R) the amino acid name , the ending –ine changed to –yl, and terminating in the COOH end AA name.

E. g. ala-gly is alanyl-glycine

19-15

Names-cont.

Glutathione: the reduced formReduces oxidizing agents by dimerizing toform the disulfide bond with release of 2 H.

SHCH2

CH CH2CH2C

O

NH CH C

OCOO-

NH3

+NH CH2COO

-

-glutamyl-L-cysteineylglycine

N-terminal C-terminal

19-16

Draw: alanyl-glycyl-valine (ala-gly-val)

CNH3

+C

O

NH C C

O

NH C C

O

O Draw theskeleton chain

CNH3

+C

O

NH C C

O

NH C C

O

O

H H H Add hydrogens

CNH3

+

HC

O

NH C C

O

NH C CCH3 CH

O

O

H H H

CH3 CH3

Add R groups

19-17

19.4 Primary StructureThe primary structure of a protein is the

amino acid sequence of the chain.

Primary structures are translations of information contained in the genes.

19-18

19.5 Secondary StructureThe two very important secondary

structures of proteins are:

-helix

-pleated sheet

Both depend on hydrogen bonding between the amide H and the carbonyl O further down the chain or on a parallel chain.

19-19

Helix

Insert Fig 19.5With caption

19-20

B Sheet: Lewis Structure

CH

C

N

CH

C

N

CH

C

N

O

H

H

O

H

O

N-term

C-term C-term

N-term

CH

C

N

CH

C

N

CH

C

N

O

H

H

O

H

O

Parallel sheet

CH

C

N

CH

C

N

CH

C

N

O

H

H

O

H

O

N-term

C-term

C-term

N-term

CH

C

N

CH

C

N

CH

C

N

O

H

H

O

H

O

Antiparallel sheet

19-21

Types of Protein Structure 1Fibrous proteins exist as long stranded molecules: Eg. Silk, collagen, wool. A colagen segment in space-filling mode illustrates this point.

Red spheres represent oxygen, grey carbon, and blue nitrogen

19-22

Types of Protein Structure 2Globular proteins have somewhat spherical shapes. Most enzymes are globular. Eg. myoglobin, hemoglobin. Myoglobin in space-filling mode is the chosen example.

19-23

19.6 Tertiary StructureThe configuration of all the atoms in the

protein chain:

side chains

prosthetic groups

helical and pleated sheet regions

19-24

Tertiary Structure: 2Protein folding attractions:1. Noncovalent forces

a. Inter and intrachain H bondingb. Hydrophobic interactionsc. Electrostatic attractions

+ to - ionic attractiond. Complexation with metal ionse. Ion-dipole

2. Covalent disulfide bridges

19-25

Tertiary interactions: diag.

NH3

+

Polypeptide Chain

COO CH2 S

CH2S

O HC

O O

CH3CH3

CH2OHCH2 OH

CHCH3 CH3CHCH3 CH3 CO

ONH3

+

Mg2+

ionic

disulfide

hydrophobicH bondsor dipoleIon-dipole

metal coord’n

19-26

19.7 Quaternary StructureQuaternary structure is the result of

noncovalent interactions between two or more protein chains.

In some cases the quaternary structure involves binding to a nonprotein group called a prosthetic group.

Hemoglobin has four protein chains and the heme prosthetic group.

19-27

19.8 Overview of Structure and Function

The combination of 1o, 2o, 3o, and 4o structures lead to function.

Some proteins are fibrous and have great strength. They make up the structural parts of cells.

Some proteins are globular and serve as transport, regulatory and enzyme proteins.

19-28

19.19 Myoglobin and HemoglobinHemoglobin transports oxygen to the cells

while myoglobin stores oxygen in skeletal muscle. Both use the heme group to bind oxygen.

Myoglobin has a single protein chain while hemoglobin has four (2 alpha and 2 beta). Each chain has a heme unit.

19-29

The Heme Group

NN

NN

CH2CH2COO-

CH2CH2-OOC

CH3 CH3

CH

CH2

CH3

CH3 CH CH2

Fe(II)Pyrrole ring

N of HisF8 bindstofifth site onthe iron.

His E7 actsas a ”gate” for oxygen.

19-30

Myoglobin: 2o and 3o aspects

Some helical regions

Heme group with iron (orange)at the center

19-31

Hemoglobin (Hb)Oxygen binds to heme in hemoglobin

cooperatively: as one O2 is bound, it

becomes easier for the next to bind. The first oxygen causes 2,3-bisphospho-glycerate (BPG) to leave deoxyhemoglobin. This causes shape changes which favor more reaction with oxygen.

H+ produced by metabolizing cells (low pH) favors oxygen release from Hb and higher pH in the lungs favors binding of oxygen to Hb.

19-32

Hemoglobin: ribbons + hemesEach chain is in ribbon form and color coded.

The heme groups are in space filling form

19-33

Oxygen Transport: Mother-FetusFetal Hb is different from maternal Hb. It does

not bind BPG and therefore has a higher affinity for oxygen. This makes for more efficient oxygen transfer!

Sickle cell hemoglobin (Hb S) has a valine substituted for a glutamic acid in the beta chain. This results in the deoxy version clumping and forming the characteristic sickle cells. People with the disease usually die young but those with only one copy of the gene (sickle cell trait) tend to resist maleria.

19-34

19.10 Protein DenaturationDenaturing destroys the physiological

function of the protein (remove the 2o-4o interactions)..

Heat (coagulation)

Change in pH leads to coagulation or unfolding to to charge repulsion.

Heavy metals

Detergents

Organic solvents

19-35

19.11 Protein Digestion and DietDigestion:

Stomach: pepsin

S. I.: trypsin, chymotrypsin, elastase, etc.

Essential Amino Acids:

Cannot be synthesized by humans

Include: Ile, Leu, Lys, Met, Phe, Thr, Try, Val

Complete protein from animals provides esential AA in proper proportions.

Incomplete protein from vegetable sources must be balanced. E. g. beans (lys + trp) and corn (met)

19-36

THE END

Protein Structure

And Function