The Structure and Function of

Large Biological Molecules

Lecture #3 Amino Acids and Proteins
Campbell Reece, Eighth Edition

Reading Assignment:
Ch t
Chapters
5

BIOL 201A
Spring 2009
Ralph Feuer

Important Notes
ImportantNotes
A
Acopyofthetext(Campbell
copy of the text (Campbell Reece,Eight
Reece Eight
Edition)willbemadeavailableinthelibrary
CDincludesanimation,videos,selftesting
CD includes animation videos self testing

MasteringBiology
MBFEUER29702:Biology201A
Practicequizthisweek

Functional Groups
Here R represents the rest of the molecule

QuickTime and a
TIFF (LZW) decompressor
are needed to see this picture.

Ethanol

OH

H O H

QuickTime and a
TIFF (LZW) decompressor
picture.
are needed to see this p

H C C C H
H H H

Acetone

QuickTime and a
TIFF (LZW) decompressor
are needed to see this p
picture.

H C C
H

OH

Acetic Acid

Organic compounds can contain atoms other than C and H; these form
Functional Groups characterized by the types of atoms present and the
way they are bonded giving these groups special properties. Bonds between
C and O or N are polar covalent bonds, and can form Hydrogen Bonds.

Linking Functional Groups

Polymers

Organic
Or
nic m
molecules
l cul s with
ith certain
c rt in functi
functional
n l groups
r ups c
can
n be
b joined
j in d b
by a
covalent bond formed when a molecule of water is removed; this
allows the creation of new types of organic molecules.

An ester is formed by combining

an alcohol and a carboxylic acid.
acid

O
R OH + HO-P-OH
R-OH
HO P OH
O-

An amide is formed by combining

an amine and a carboxylic acid.
acid

O
R O P OH + H2O
R-O-P-OH
O-

A
A phosphoester is formed from an alcohol and phosphoric acid.
acid
More than one phosphoester bond can be formed in this way linking
two molecules together

Fig. 4.6: Ester

bonds link fatty acid carboxyl groups to

OH-- groups of Glycerol
OH
Fat droplets (stained red)

100 m
A fat molecule

Mammalian adipose cells

Transesterification
AlcoholsandEsters
Transesterification:
T
t ifi ti
alcohol
l h l + ester
t
different alcohol + different ester
Transesterification is used in the
synthesis of polyester
Polyester is a category of polymers
which contain the ester functional
group
g
p in their main chain
John Rex Whinfield and James Tennant
Dickson (1941)

The Structure and Function of

Large Biological Molecules
Lecture #3 Amino Acids and Proteins
Campbell Reece, Eighth Edition

Reading Assignment:
Ch t
Chapters
5

BIOL 201A
Spring 2009
Ralph Feuer

Outline
IV. -Amino Acids: carboxyl and amino groups bonded to -Carbon
A. Acid/Base properties
1. carboxyl group is proton donor weak acid
2. amino group is proton acceptor weak base
3 At physiological
3.
h i l i l pH:
H H3N+-C-COO
C COOB. Ca is tetrahedral and bonded to 4 different groups
1. L configuration for all natural amino acids (few exceptions)
2. 20 different R groups
C. Classification based on R-group - know one example from each
p
y p
2. Aromatic-hydrophobic
y p
1. Aliphatic-hydrophobic
3. Polar Uncharged-hydrophilic
4. Acidic-hydrophilic
5. Basic-hydrophilic

V. Polypeptides and Proteins

A. Peptide Bond
1. join amino group of one amino acid with carboxyl group of another by forming
and amide bond between them Peptide Bond
2 C
2.
C-N
N bond has partial double bond character
B. Peptides and Polypeptides
1. Peptides contain relatively few amino acids linked by peptide bonds: dipeptide,
tripeptide, tetrapeptide, .
2. Polypeptide contains many amino acids and if there are very many amino acids
one can call it protein
C P
C.
Proteins
i have
h
molecular
l
l weights
i h > severall thousand
h
d and
d have
h
3-4
3 4 llevels
l off
structure
1. Primary Structure (1) sequence of amino acids connected by peptide bonds
2. Secondary Structure (2) local conformation of peptide bond backbone stabilized
by H-bonds: -helix: intrachain H-bonds & -sheet: interchain H-bonds
3. Tertiary Structure (3): The complete 3-dimensional structure described by the
way the polypeptide chain folds back on itself; stabilized by interactions (bonds)
between the amino acid R-groups. Hydrophobic Bonds & van der Walls
Interactions most important
4. Quaternary Structure (4): only some proteins have 4 structure which is the
association of more than one polypeptide

Overview:TheMoleculesofLife
Alllivingthingsaremadeup
offourclassesoflarge
biologicalmolecules
g
carbohydrates,lipids,
proteins,andnucleicacids

Within
Withincells,smallorganic
cells small organic
moleculesarejoined
together
formlargermolecules

Macromolecules
largemoleculescomposed
ofthousandsofcovalently
f th
d f
l tl
connectedatoms

Molecular
Molecularstructureand
structure and
functionareinseparable

Concept5.1:Macromoleculesarepolymers,built
frommonomers
Polymer
Longmoleculeconsistingof
g
g
manysimilarbuildingblocks

These
Thesesmallbuildingblock
small building block
moleculesarecalled
monomers
Threeofthefourclassesof
lifesorganicmoleculesare
g
polymers:
Carbohydrates
Proteins
Nucleicacids

TheSynthesisandBreakdownofPolymers
Acondensationreaction

HO

Dehydration
Dehydrationreaction
reaction
Occurswhentwo
monomersbond
togetherthroughtheloss
of a water molecule
ofawatermolecule

HO

Unlinked monomer

Dehydration removes a water

molecule, forming a new bond

Enzymes

H2 O

Longer polymer
(a) Dehydration reaction in the synthesis of a polymer

Macromolecules
Macromoleculesthat
that
speedupthe
dehydrationprocess

HO

Polymers

Hydrolysis adds a water

molecule, breaking a bond

Disassembledto
monomersbyhydrolysis,
Reactionthatis
Reaction
that is
essentiallythereverseof
thedehydrationreaction

Short polymer

HO

HO

(b) Hydrolysis of a polymer

H2 O

HO

HO

Short p
polymer
y

HO

Unlinked monomer

Dehydration removes a water

molecule forming a new bond
molecule,

HO

H2O

Longer polymer
( )
(a)

D h d ti reaction
Dehydration
ti iin th
the synthesis
th i off a polymer
l

HO

Hydrolysis adds a water

molecule, breaking a bond

HO
(b)

Hydrolysis of a polymer

H2O

HO

TheDiversityofPolymers
Eachcellhasthousands
of different kinds of
ofdifferentkindsof
2
macromolecules
Macromoleculesvary
y
amongcellsofan
organism,varymore
withinaspecies,and
vary even more between
varyevenmorebetween
species
An
Animmensevarietyof
immense variety of
polymerscanbebuilt
fromasmallsetof
monomers

HO

Amino Acids / Peptides / Proteins

Complex Polymer
(Macromolecule)
Polysaccharide
(Complex Carbohydrate)

Monomer

Simple Polymer

Monosaccharide
(Sugar)

Oligosaccharide

Nucleotide

Oligonucleotide

Nucleic Acid

Peptide

Polypeptide
Protein

Amino Acid

Concept5.4:Proteinshavemanystructures,
resulting in a wide range of functions
resultinginawiderangeoffunctions
Proteins
accou
accountformorethan50%of
t o o e t a 50% o
thedrymassofmostcells

Proteinfunctions
P t i f ti

Antibody protein

Structuralsupport
Storage
Transport
Cellularcommunications
Movement
Defenseagainstforeign
substances

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Protein from flu virus

TheCatalyticCycleofanEnzyme
Enzymes
Type
Typeofprotein
of protein
Actsasacatalyst to
speedupchemical
reactions

Substrate
(sucrose)

Glucose

Enzymescanperform
theirfunctions
repeatedly,functioning
asworkhorsesthat
carry out the processes
carryouttheprocesses
oflife

OH
Fructose
HO

Enzyme
(sucrase)
H2O

PolypeptidesAndAminoAcidMonomers
Polypeptidesare
polymersbuiltfromthe
same set of 20 amino
samesetof20amino
acids

carbon

Aproteinconsistsofone
ormorepolypeptides
Aminoacidsareorganic
moleculeswithcarboxyl
andaminogroups
g p
Aminoacidsdifferintheir
propertiesdueto
differingsidechains,
g
,
calledRgroups

Amino
group

Carboxyl
group

20 Different Amino Acids

Are Found in Proteins
A
C
D
E
F
G
H
I
K
L

Alanine:
Ala
Cysteine:
Cys
Aspartic acid: Asp
Glutamic acid: Glu
Phenylalanine: Phe
Glycine:
Gly
Histidine:
d
His
Isoleucine:
Ile
Lysine:
Lys
Leucine:
Leu

One
Full name
letter
symbol

Three
letter
symbol

M
N
P
Q
R
S
T
V
W
Y

Methionine: Met
Asparagine: Asn
Proline:
Pro
Glutamine: Gln
Arginine:
Arg
Serine:
Ser
Threonine:
h
Thr
h
Valine:
Val
Tryptophan: Trp
Tyrosine:
Tyr

Each
E
h amino
mi acid
id can
be designated by a 3-letter
or 1-letter abbreviation

Nonpolar

Glycine
(Gly or G)

Valine
(Val or V)

Alanine
(Ala or A)

Methionine
(Met or M)

Leucine
(Leu or L)

Trypotphan
(Trp or W)

Phenylalanine
(Phe or F)

Isoleucine
(Ile or )

Proline
(Pro or P)

Polar

Serine
(Ser or S)

Threonine
(Thr or T)

Cysteine
(Cys or C)

Tyrosine
(Tyr or Y)

Asparagine Glutamine
(Asn or N) (Gln or Q)

Electrically
charged
A idi
Acidic

Aspartic acid Glutamic acid

(Glu or E)
(Asp or D)

B i
Basic

Lysine
(Lys or K)

Arginine
(Arg or R)

Histidine
(His or H)

NonpolarandPolarCovalentBonds
Inanonpolar covalent
bond,theatomsshare
the electron equally
theelectronequally
Inapolarcovalent
b d
bond,oneatomismore
t
i
electronegative,andthe
atomsdonotsharethe
electron equally
electronequally
Unequalsharingof
electronscausesa
l t
partialpositiveor
negativechargeforeach
atom or molecule
atomormolecule

Fig. 5.17: Non

Non--polar, hydrophobic aliphatic and aromatic amino acids often
cluster together and are found in the interior of proteins

Aliphatic

W
Aromatic
Y

Polar amino acids contain functional groups in their side chains that can
Hydrogen Bond with other groups.
They are hydrophilic and often found on the surface of proteins

Polar
P
l
Uncharged

Acidic

Basic

Polar
Charged
g

Amino Acids with Hydroxyl Groups in their Sidechains

(S, T, Y)

These amino acids can also be modified by phosphorylation

((addition of p
phosphate
p
to the hydroxyl
y
y group)
g
p)
O-

Side chain-O-H

Side chain-O-P-OO

Amino Acids that Carry a Charge in their side chain at

neutral pH (D,
(D, E,
E, K, R, H)
H)

Negatively charged
Acidic

Have a carboxyl
group in their side
chain

Positively charged
Basic

Have N
N+ group
in their side chain

Asparagine (N) is a derivative of Aspartic acid (D)

Note:
similar size and shape
but different
D chemical properties

Glutamine (Q) is a derivative of Glutamic acid (E)

Aromatic side chains (F,W,Y)

Ring system in side chain absorbs ultra-violet (UV) light

giving us a way of measuring protein concentration
Note similar size and shape of Tyr and Phe
(only difference is extra OH group in Tyr
making
ki it more h
hydrophilic)
d
hili )

Special cases:
Glycine is the smallest amino acid and its small
side chain can fit into small spaces in protein

The sulfhydryl group (-S-H) of two

cysteines can react to form a covalent
di lfid b
disulfide
bridge
id ((-S-S-)
S S )
The side
Th
id chain
h i of
f proline
li is
i covalently
l tl
linked back to the -amino group. This
limits the rotation of
f the side chain and
introduces kinks in proteins

Phenylalanine

Phenylketonuria
Geneticdisorder
i di d
Inabilitytometabolize
phenylalanine
Autosomal recessivegenetic
disorder
Deficiencyintheenzyme
phenylalaninehydroxylase
Necessarytometabolize
phenylalanineintotyrosine

Leftuntreated,maycausebrain
developmentproblems
Mentalretardation
Seizures

Controlledbydiet

Phenylketonurics:Contains
phenylalanine
phenylalanine

Tryptophan
Plentifulinredmeat,,
eggs,chocolate,seeds,
poultry
Functionsasa
biochemical precursor
biochemicalprecursor
forserotonin
Neurotransmitter
Modulationofanger,
aggression,sleep,
appetite

Aspartame

Artificialsweetener

Dipeptide
Methylesterofasparticacidand
phenylalanine

EqualorNutraSweet

Somecontroversyoversafety
Affectmentalprocesses?
Cancer

2007 Safety Evaluation

2007SafetyEvaluation
Aspartameissafeatcurrentlevels
ofconsumption
MagnusonBA,BurdockGA,Doull J,
etal(2007)."Aspartame:asafety
evaluationbasedoncurrentuse
l ti b d
t
levels,regulations,andtoxicological
andepidemiologicalstudies".Crit.
Rev.Toxicol.37(8):629727

AminoAcidPolymers
Aminoacidsarelinkedby
peptide bonds
peptidebonds

Peptide
bond

Apolypeptideisapolymer
ofaminoacids
(a)

Polypeptidesrangeinlength
range in length
Polypeptides
fromafewtomorethana
thousandmonomers

Side chains
Peptide
bond

B kb
Backbone

Eachpolypeptidehasa
uniquelinearsequenceof
amino acids
aminoacids

(b)

Amino end
(N-terminus)

Carboxyl end
(C-terminus)

ProteinStructureandFunction

Afunctionalproteinconsistsofoneor
morepolypeptidestwisted,folded,
andcoiledintoauniqueshape

Thesequenceofaminoacids
determinesaproteinsthree
dimensional structure
dimensionalstructure

Aproteinsstructuredeterminesits
function

Foldingputssomeaminoacidside
chains(Hydrophobic)ininteriorand
some (Hydrophilic) on exterior surface
some(Hydrophilic)onexteriorsurface
ofprotein

Groove

(a) A ribbon model of lysozyme

Groove

Differentfunctionalgroupsonsurface
givelocalsitesdistinctshapesand
i l l it di ti t h
d
specificproperties
(b) A space-filling model of lysozyme

FourLevelsofProteinStructure

Theprimarystructureofaproteinisitsuniquesequenceofaminoacids
determinedbyinheritedgeneticinformation

Secondarystructure,foundinmostproteins,consistsofcoilsandfoldsinthe
polypeptidechain

y
y
g
( g p)
Tertiarystructureisdeterminedbyinteractionsamongvarioussidechains(Rgroups)

Quaternarystructureresultswhenaproteinconsistsofmultiplepolypeptidechains
Primary
P
i
Structure

Secondary
S
d
Structure
pleated sheet

+H N
3

Amino end
Examples of
amino acid
subunits

helix

T ti
Tertiary
Structure

Quaternary
Q
t
Structure

Describing Macromolecular Structure

Protein structure can be described on five levels:
1 Monomers: the
1.
th amino
min acid
id building
buildin blocks
bl ks
2. Primary structure (1): the sequence in which the
monomers (amino acids) are connected

3. Secondary structure (2):

local ways of folding polymer

4. Tertiary structure (3): the overall fold of the molecule

(its three dimensional shape or conformation)

5. Quaternary structure (4):

intermolecular associations

SecondaryStructure
Coilsandfoldsof
secondary structure
secondarystructure
Resultfromhydrogen
Secondary Structure
pleated sheet
bondsbetweenrepeating
constituentsofthe
f h
Examples of
amino acid
polypeptidebackbone
subunits

Typicalsecondary
structures
Coilcalledan helix
Foldedstructurecalleda
pleatedsheet
l t d h t

helix

Abdominal g
glands of the
spider secrete silk fibers
made of a structural protein
containing
gp
pleated sheets.
The radiating strands, made
of dry silk fibers, maintain
the shape of the web
web.
The spiral strands (capture
strands)
t
d ) are elastic,
l ti stretching
t t hi
in response to wind, rain,
and the touch of insects.
Spider silk is a remarkably strong material. Its tensile strength is superior to
that of high-grade steel, and as strong as Aramid filaments, such as
Twaron or Kevlar.
Most importantly, spider silk is extremely lightweight: a strand of spider silk
long enough to circle the earth would weigh less than 16 ounces

TertiaryStructure
Tertiarystructure
Determinedbyinteractions
between R groups rather
betweenRgroups,rather
thaninteractionsbetween
backboneconstituents
Tertiary Structure

InteractionsbetweenRgroups

Hydrogenbonds
Ionicbonds
Hydrophobicinteractions
Vander Waalsinteractions

SStrongcovalentbondscalled
l
b d
ll d
disulfidebridgesmay
reinforcetheproteins
structure

Quaternary Structure

Fig. 5.20:

What Stabilizes Tertiary Structure?

1. Hydrophobic and van derWaals

Interactions: Packing (clustering)
of hydrophobic side chains into
interior away from water, keeping
most hydrophilic side chains on
surface.
2. Hydrogen bonds of secondary
structure elements
3. Ionic interactions between
oppositely charged side chains
4. Some proteins are also
stabilized by disulfide bridges
between pairs of cysteine side
chains

Fig. 3.9:

What types of Chemical Bonds are important in the Four

Levels of Protein Structure

Level of
Structure
Primary
Secondary
Tertiary

Type of Bond
Covalent Peptide Bond
Hydrogen Bond

Between peptide
bond groups

Hydrophobic Bond most

important + others

Quaternary Hydrophobic Bond most

important + others

Polypeptide
chain

Chains

Iron
Heme
Chains
g
Hemoglobin
Collagen
Main protein of connective tissue in animals
and the most abundant protein in mammals

The iron-containing oxygen-transport

metalloprotein in the red blood cells of vertebrates

QuaternaryStructure
Quaternarystructure
resultswhentwoormore
polypeptide chains form
polypeptidechainsform
onemacromolecule

Polypeptide
chain

Chains

Collagen
g
Fibrousproteinconsisting
ofthreepolypeptides
coiledlikearope

Hemoglobin
Globularproteinconsisting
of four polypeptides
offourpolypeptides
twoalphaandtwobeta
chains

Iron
Heme
Chains
Hemoglobin
g
Collagen
Main protein of connective tissue in animals
and the most abundant protein in mammals

The iron-containing oxygen-transport

metalloprotein in the red blood cells of vertebrates

Proteins Form a Variety of Shapes and Sizes

Classification by use of Secondary Structure

Myoglobin
all -helix

Flavodoxin
Fl
d i
-helix & -sheet

Antibodies
A
tib di
all -sheet

Quaternary Structure: Some proteins form stable oligomeric

structures containing two or more polypeptides

Antibodies
Hemoglobin

Photosynthetic
Reaction Center
(membrane protein)

Cofactors: Some proteins bind ions and/or organic molecules

to help them fulfill their function
Myoglobin stores O2
Hemoglobin transports O2
Note the similar tertiary
structures.
t
t
Both use Heme cofactors
to bind O2

Hemoglobin

Myoglobin

WhatCanthe3DShapeofanEnzymeTellUsAboutFunction

ScientistsuseXraycrystallography
todetermineaproteinsstructure
RogerKornberg(NobelPrizeWinner
2006)
Xraydiffractionpatterns

3Dmodelofthecomplex
Assistanceofcomputersoftware

Diffracted
X-rays
X-ray
source X-ray
beam
Crystal

Anothermethodisnuclearmagnetic
resonance(NMR)spectroscopy,
Doesnotrequireproteincrystallization
Usedtoobtainphysical,chemical,
Used to obtain physical, chemical,
electronicandstructuralinformation
aboutmoleculesduetothechemical
shiftandZeemaneffectonthe
resonantfrequenciesofthenuclei

EXPERIMENT

Bioinformaticsusescomputer
programstopredictprotein
structurefromaminoacid
q
sequences

Digital detector

X-ray diffraction
pattern

RESULTS
RNA
polymerase
DNA

RNA

SickleCellDisease:AChangeinPrimaryStructure
Aslightchangein
primarystructure
canaffecta
proteinsstructure
andabilityto
d bilit t
function
Sicklecelldisease,
Inheritedblood
disorder,results
f
fromasingle
i l
aminoacid
substitutionin
theprotein
p
hemoglobin

Normal hemoglobin
Primary
structure
t
t

Secondary
and tertiary
structures

subunit

Function

Normal
hemoglobin
(top view)

Secondary
and tertiary
structures

Val His Leu Thr Pro Val Glu

Normal red blood

cells are full of
individual
hemoglobin
moledules, each
carrying oxygen.

Sickle-cell
hemoglobin

Function

Molecules
interact with
one another and
crystallize into
a fiber; capacity
to carry oxygen
is greatly reduced.

10 m
Red blood
cell shape

subunit

Molecules do
not associate
with one
another; each
carries oxygen.

Quaternary
structure

Exposed
hydrophobic
region

Quaternary
structure

Sickle-cell hemoglobin
Primary
structure

Val HisLeu Thr Pro Glu Glu

10 m
Red blood
cell shape

Fibers of abnormal
hemoglobin deform
red blood cell into
sickle shape.

10 m

Normal red blood

cells are full of
individual
hemoglobin
molecules,, each
carrying oxygen.

10 m

Fibers of abnormal
hemoglobin deform
red blood cell into
sickle shape.

Malaria

Themostseriousinfectiousdiseaseofhumans

300600millionclinicalcasesannually

510%oftheworldspopulation

2milliondeathsannually

Sicklecellanemia

Survivalvalueincarryingsicklecellgenes

Heterozygoteindividualshavemostlyminorproblems
Homozygousindividuals

Protozoanparasite
TransmissiontovertebratehostsbyfemaleAnopheles
mosquito

Typicallycausesabenigninfection

Infectionoflivercells

Shortenedlifeexpectancy
Variouspainfulepisodes

Plasmodium (four species)

Plasmodium(fourspecies)

Sickleredbloodcellsnotconducivetotheparasite

Clinicalsilent

Mostcasesofseveredisease

Plasmodiumfalciparum

Bloodstagecycle

WhatDeterminesProteinStructure?

Inadditiontoprimarystructure,
physicalandchemicalconditions
canaffectstructure

AlterationsinpH,salt
concentration,temperature,or
otherenvironmentalfactorscan
causeaproteintounravel
i
l

Thislossofaproteinsnative
structureiscalleddenaturation

Adenaturedproteinisbiologically
inactive

Informationfordetermining
specificfoldingiscontainedwithin
theproteinprimarysequence
Anfinsenexperiment(1965)

Denaturation

Normal protein

Renaturation

Denatured protein

ProteinFoldingintheCell
Itishardtopredicta
proteinsstructure
from its primary
fromitsprimary
structure
Mostproteins
probablygothrough
severalstatesontheir
waytoastable
t
t bl
structure
Chaperonins
Proteinmoleculesthat
assisttheproper
f ldi
foldingofother
f th
proteins

Polypeptide

Correctly
folded
protein
t i

Cap

Hollow
cylinder

Chaperonin
(fully assembled)

Steps of Chaperonin 2 The cap attaches, causing the 3

The cap comes
Action:
cylinder to change shape in off, and the properly
such a way that it creates a
folded protein is
1
An unfolded polyreleased.
peptide enters the hydrophilic environment for
cylinder from one end. the folding of the polypeptide.