Transcript Protein Structure

Power Point to Accompany
Principles and Applications of
Inorganic, Organic, and
Biological Chemistry
Denniston, Topping, and Caret
4th ed
Chapter 19
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
19-1
Introduction
Proteins:
Provide nitrogen and sulfur for the diet
Most abundant macromolecules in the
cell
Carry out most of the work of the cell
19-2
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
19-3
Four Levels of Protein Structure
Primary, 1o
the amino acid sequence
Secondary, 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 19-4
19.2 The a-Amino Acids
An 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.
Generic amino
acid at physiological
pH.
H O
+
H3 N C C O
aC
R1
19-5
If the R group is not H, the AA can exist
in two enantiomeric forms
(nonsuperimposable mirror image)
forms.)
O
a carbon
O
C
+
H3N C H
R1
O
O
C
+
H C NH3
R1
Mirror plane
Amino acids incorporated into
proteins have the L- configuration.
19-6
AA with nonpolar side chains-1
H
H
+
+
H3N C COO H3N C COO
CH2
CH3
alanine, ala phenylalanine,
Phe
H
H
+
+
H3N C COO H3N C COO
CH2
CH3CH
CH
CH2
CH3 CH3
CH3
leucine,leu isoleucine, Ile
19-7
AA with nonpolar side chains-2
H
H
+
+
H3N C COO
H3N C COO
CH2CH2 S CH3
CH3 CH CH3
valine, val
methionine, Met
H
H
+
+
H2N C COO
H3N C COO
CH
2
CH
CH2
2
C
CH2
CH
N
proline, Pro
H
tryptophan, Trp
19-8
AA with polar side chains-1
H
H
+
+
H3N C COO
H3N C COO
H
CH2 OH
glycine, gly
serine, ser
H
+
H3N C COO
CH2 SH
cysteine, cys
H
+
H3N C COO
CH OH
CH3
threonine, thr 19-9
AA with polar side chains-2
COO
+
H3N C H
CH2
C
O
NH2
asparagine, Asn
COO
+
H3N C H
CH2
COO
+
H3N C H
CH2
CH2
O C NH2
glutamine, Gln
tyrosine, Tyr
OH
19-10
AA: acidic and basic
-
+ COO
-
+ COO glutamic
H3N C H aspartic H3N C H
CH2 acid,
CH2 acid, Asp
CH2 Glu
C
O
O
O -C O
+ COO
+ COO
+ COO
H3N C H
H3N C H
H3N C H
CH2
CH2
H CH2
CH2
CH2
C+ C
CH2
CH2
HN
NH
CH
+ NH
C
+ 2
H2N C NH2
H
H3N
arginine, Arg
lysine, Lys
histidine, His 19-11
19.3 The Peptide Bond
A 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.
H O
H O
H O
+
+
+
H3 N C C O H3 N C C O H3 N C C O
R1
-H2O
R1
-H2O
R1
H O
H O
H O
+
H3 N C C N C C N C C O
H
H
R1
R1
R1
Peptide bonds
19-12
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.
+
H3N
CH
R
O
C
+
H
N
C
H3N
CH
R
O
C
-
+
H
N
C
19-13
Peptides: Structure and Names
Structure 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 a-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
19-14
Names-cont.
N-terminal
-
COO
C-terminal
O
O
+
-
H3 N CH CH2 CH2 C NH CH C NH CH2COO
CH2
SH
-glutamyl-L-cysteineylglycine
Glutathione: the reduced form
Reduces oxidizing agents by dimerizing to
form the disulfide bond with release of 2 H.
19-15
Draw: alanyl-glycyl-valine (ala-gly-val)
O
O
O
+
Draw the
H3N C C NH C C NH C C O
skeleton chain
HO
HO
HO
Add hydrogens
+
H3N C C NH C C NH C C O
HO
HO
HO
Add R groups
+
H3N C C NH C C NH C C O
CH3
H
CH
CH3 CH3
19-16
19.4 Primary Structure
The primary structure of a protein is the
amino acid sequence of the chain.
Primary structures are translations of
information contained in the genes.
19-17
19.5 Secondary Structure
The two very important secondary
structures of proteins are:
a-helix
b-pleated sheet
Both depend on hydrogen bonding
between the amide H and the
carbonyl O further down the chain
or on a parallel chain.
19-18
a Helix
Insert Fig 19.5
With caption
19-19
B Sheet: Lewis Structure
N-term
C-term
CH
C O
H N
HC
O C
N H
CH
C O
H N
HC
H N
C O
CH
N H
O C
HC
H N
C O
C-term
N-term
Antiparallel sheet
N-term
CH
C O
H N
HC
O C
N H
CH
C O
H N
C-term
N-term
CH
C O
H N
HC
O C
N H
CH
C O
H N
C-term
Parallel sheet
19-20
Types of Protein Structure 1
Fibrous 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
19-21
Types of Protein Structure 2
Globular proteins have somewhat spherical
shapes. Most enzymes are globular. Eg.
myoglobin, hemoglobin. Myoglobin in spacefilling mode is the chosen example.
19-22
19.6 Tertiary Structure
The configuration of all the atoms in the
protein chain:
side chains
prosthetic groups
helical and pleated sheet regions
19-23
Tertiary Structure: 2
Protein folding attractions:
1. Noncovalent forces
a. Inter and intrachain H bonding
b. Hydrophobic interactions
c. Electrostatic attractions
+ to - ionic attraction
d. Complexation with metal ions
e. Ion-dipole
2. Covalent disulfide bridges
19-24
Tertiary interactions: diag.
disulfide
+
NH3 O
O C
Polypeptide Chain
CH2 S
S CH2
CH3
CH3
HO CH2
CH2 OH
metal coord’n
Mg2+
H3C CH CH3
O O
H3C CH CH3
O H C
ionic
Ion-dipole
hydrophobic
+
NH3 O
O C
H bonds
19-25
or dipole
19.7 Quaternary Structure
Quaternary 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.
19-26
19.8 Overview of Structure and Function
o
o
o
o
The combination of 1 , 2 , 3 , and 4
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.
19-27
19.19 Myoglobin and Hemoglobin
Hemoglobin 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.
19-28
The Heme Group
-
-
CH2CH2COO
OOC CH2CH2
N of His
F8 binds
CH3
H3C
to
N
N
fifth site on
the iron.
Fe(II)
Pyrrole ring
H2C
N
N
CH
CH3
His E7 acts
as a ”gate”
CH3
CH CH2
19-29
for oxygen.
Myoglobin:
o
2
and
o
3
aspects
Some helical regions
Heme group with iron (orange)
19-30
at the center
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-bisphosphoglycerate (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.
19-31
Hemoglobin: ribbons + hemes
Each chain is
in ribbon
form and
color coded.
The heme
groups are in
space filling
form
19-32
Oxygen Transport: Mother-Fetus
Fetal 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
19-33
maleria.
19.10 Protein Denaturation
Denaturing destroys the physiological
function of the protein (remove the 2o4o interactions)..
Heat (coagulation)
Change in pH leads to coagulation or
unfolding to to charge repulsion.
Heavy metals
Detergents
Organic solvents
19-34
19.11 Protein Digestion and Diet
Digestion:
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)
19-35
and corn (met)
THE END
Protein Structure
And Function
19-36