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Advanced Biochemistry and
Chemical Biology
CHM4034 Spring 2008
• Dr. Lyons office hours
[email protected]
846-3392
- W 10-11 AM
- T,R 4:00-5:00 PM
Class website http://www.chem.ufl.edu/~lyons/
2
1
3
4
5
6
7
Greek lettering scheme used to identify the atoms in amino
acid side chains
An a-amino acid
Non-polar, aliphatic
g1
H
b
HS
C a
+H3N
a
C
H
O-
O-
H
CH
O-
Ca
C
C
O
O
Glycine
Alanine
CH3
b
+H3N
O
g2
CH3
Ca
+H3N
H3C
Valine
Non-polar, aliphatic
d1
H3C
H
CH3
d2
H3C
H
C
C a
OC
+H3N
d
CH2CH3
CH2
C a
+H3N
g
CH
b
g1
g2
b
H
O-
C
O
O
Leucine
Isoleucine
Non-polar, aliphatic
H
b
CH2
Ca
+H3N
g
CH2
O-
d
S
e
CH3
g
CH2
H
d
O
CH2
H2C
C
C
b
N+
H2
a
OC
O
Methionine
Proline
Aromatic
e1
e1
d1
e2
H
C
+H3N
d2
e2
g
b
CH2
a
H
O+H3N
Phenylalanine
d2
CH2
Ca
C
O
z1
d1
g
b
h
OH
z1
OC
O
Tyrosine
Aromatic
e1
H
N
d1
e2
z2
g
H
b
CH2
C
+H3N
a
OC
O
h
d2
e3
z3
Tryptophan
Polar, uncharged
g
OH
b
H
C
+H3N
a
H
O-
CH2
C a
C
O
SH
b
CH2
+H3N
Cysteine
H
C
C
C
+H3N
CH3
b
H
O-
O
Serine
g2
g
a
OH g1
O-
C
O
Threonine
Polar, uncharged
e1
e1
d1
O
d1
O
C
C
b
H
CH2
C
+H3N
g
a
NH2
d2
b
H
C
+H3N
g
CH2
O-
C
H2C
a
NH+
NH2
d
e2
H
b
C
O-
C
HN
+H3N
g
CH2
a
O-
C
O
O
O
Asparagine
Glutamine
Histidine
d2
e2
Positively Charged
H
h2
CH2
NH
NH2+
b
CH2
C
+H3N
g
e
a
CH2
C
d
O-
C
O
Arginine
z
e
g
CH2
CH2
H
H2N
b
CH2
Ca
h1
+H3N
CH2
d
O-
C
O
Lysine
NH3+
z
Negatively Charged
d1
e1
O
O
H
b
C
+H3N
C
CH2
a
C
O
Aspartate
g
O-
O-
C
d2
H
b
C
+H3N
H 2C
CH2
a
g
O-
C
O
Glutamate
d
O-
e2
Alanine
Cysteine
Glycine
Histidine
Isoleucine
Leucine
Methionine
Proline Pro
Serine
Threonine
Valine
Ala
Cys
Gly
His
Ile
Leu
Met
P
Ser
Thr
Val
A
C
G
H
I
L
M
S
T
V
Arginine
Asparagine
Aspartate
Glutamate
Glutamine
Lysine
Phenylalanine
Tryptophan
Tyrosine
Arg
Asn
Asp
Glu
Gln
Lys
Phe
Trp
Tyr
R
N
D
E
Q
K
F
W
Y
Non-standard encoded amino acids
-OOC
H
C
a
CH2
Selenocysteine
Sec, U
SeH
+
NH3
-OOC
O
H
C
a
CH2 CH2
CH2
CH2
H
N
CH3
NH3+
N
Pyrrolysine
Pyl, O
Amino acids bear structural similarity to each other
Asparate
Glutamate
d1
-OOC
H
C
b
CH2
C
g
H
O-
+
NH3
d2
Asparagine
-OOC
b
CH2
C
+
NH3
C
O
a
b
g
CH2
CH2
NH3+
d
e2
Glutamine
e1
O
-OOC
C g
NH2
d2
C
O-
d1
O
a
H
-OOC
O
a
e1
H
a
C
b
g
CH2 CH2
+
NH3
d
C
NH2
e2
Amino acids bear structural similarity to each other
Cysteine
Selenocysteine
-OOC
-OOC
H
C
a
b
g
CH2
SH
a
H
C
CH2
SeH
+
NH3
+
NH3
Threonine
Serine
-OOC
H
a
H
-OOC
b
C
C
CH3
g2
+H3N
OH
g1
a
H
C
+
NH3
b
g
CH2
OH
Amino acids bear structural similarity to each other
Tyrosine
d1
-OOC
H
C
b
a
CH2
+
NH3
g
e1
z1
OH
h
d2
e2
Phenylalanine
d1
-OOC
a
H
C
+H3N
b
g
CH2
e1
z1
d2
e2
Amino acids bear structural similarity to each other
H
H
Histidine
H
N
N
CH2
CH2
CH2
H
CH2
N+
Asparagine O
H
H
Histidine
H
Histidine
N
N+
N
Glutamine
HH
O
HH
H
H
CH2
+
N
N
Arginine
N
CH2
H Histidine
N
NH2+
N
CH2
CH2
Arginine
+H N
2 +
N
H
H
Amino acids bear structural similarity to each other
Histidine
H
N
CH2
CH2
Tryptophan
N+
N
HH
Amino acids bear structural similarity to each other
OH
Phenylalanine
Tyrosine
CH CH2 CH2
H3C
CH2
CH3
CH
2 2
CH
CHCH
2 2
OH
Phenylalanine
Leucine
Degeneracy prevents mutation from being deleterious
One could argue that this is how RNAP is proofread
For Phe
UUU or UUC
If you mutate almost
any position you still
end up with a
branched chain
hydrophobic amino
acid. Only U to C or U
to G at position 2
result in large
changes
Degeneracy prevents mutation from being deleterious
One could argue that this is how RNAP is proofread
For His
CAU or CAC
You change to Gln,
Arg, Asn or Asp
Asp is like His
functionally in that it
binds metal ions….
The genetic code can be expanded
Stop codons are often reassigned
UGA encodes selenocysteine, pyrrolysine
These values are the pKa’s of the free amino acids in
aqueous solution. As we shall see later an aqueous
solution may not represent reality
O
C
-O
H
H
N
CH2
O-
C
+H3N
N
C
O
H
O
CH2
These values are the pKa’s of the free amino acids in
aqueous solution. As we shall see later an aqueous
solution may not represent reality
Hydrophobic pocket
O
C
OH
Condensation of two a-amino acids to form
a dipeptide.
HN
NH+
HS
H
H
H
N
C
+H3N
O
CH2
C
O H3C
H
N
C
N
H
C
H
O
CH2
C
O
C
C
CH2
H
H
N
C
N
H
CH2
CH2
CH2
NH3+ H3C
H
N
H
H
H
O-
C
C
C
C
H
CH2
O
CH2
C
O
CH
CH3
Nterm - Histidine-alanine-cysteine-lysine-phenylalanine-leucine-glycine Cterm
Nterm - His-Ala-Cys-Lys-Phe-Leu-Gly - Cterm
Nterm - HACKFLG - Cterm
Sugars and Polysaccharides
O
1
H
O
H
C
O
C
C
2 H
C
3
CH2OH
OH
H
1
CH2OH
2
C
3
CH2OH
O
CH2OH
2
C
O
C
OH
4
H
OH
CH2OH
1
3
C
CH2OH
CH2OH
H
H
OH
Glyceraldehyde contains one chiral
center* at C-2.
In general n carbon aldoses
contain 2n-2 stereoisomers.
Dihydroxyacetone the simplest ketose, does not contain
a chiral center
Erythrulose, the second sugar in the ketose series,
contains one chiral center at C-3.
In general n carbon ketoses contain 2n-3 stereoisomers
Nomenclature :
- Fischer convention : D sugars have the same absolute configuration
at the stereogenic center farthest removed from their carbonyl group as
does D-glyceraldehyde.
O
O
H
H
H
C
C
OH
CH2OH
O
O
H
C
H
OH
H
H
OH
HO
CH2OH
H
H
C
OH
H
OH
CH2OH
H
HO
CH2OH
C
H
O
H
H
HO
O
H
C
OH
H
HO
H
C
H
OH
H
OH
HO
H
H
OH
HO
H
CH2OH
CH2OH
HO
H
H
OH
H
OH
H
OH
H
OH
CH2OH
- The L version of the sugars are the
mirror image of their D counterparts
O
OH
CH2OH
D-Arabinose
D-Xylose
•L sugars are biologicaly much less abundant than D
sugars. Know the structures of the sugars whose
names are boxed.
•Aldoses to remember are:
D-glyceraldehyde, D-erythrose, D-ribose, Dmannose, D-galactose, D-glucose
•Ketoses to remember are:
Dihydroxyacetone, D-erythrulose, D-ribulose, Dxylulose, D-fructose
Epimers
Configurations and conformations
Sugars can exist in several cyclic conformations, this is a consequence of the
intrinsic chemical reactivity of the functional groups in the corresponding sugar
O
H
H
HO
C
CH2OH
OH
H
O
HO
H
H
OH
H
OH
H
OH
H
OH
CH2OH
CH2OH
Intramolecular reactions
The reactions of alcohols with (a) aldehydes to form
hemiacetals and (b) ketones to form hemiketals.
D-glucose is 33% a and 66% b
H OH
H OH
H
H
O
HO
O
HO
H
HO
H
H
OH
HO
H
OH
OH
a glucose
H
OH
H
b glucose
b-glucose-(1,4)-b-glucose
glucose-(b14b)-glucose
a-glucose-(1,4)-b-glucose
glucose-(a14b)-glucose
a-glucose-(1,6)-a-glucose
glucose-(a1a)-glucose
Trehalose
CH2OH
O
a-glucose-(1,1)-a-glucose
OH
OH
O
O
OH
HO2HC
OH
OH
OH
glucose-(a11a)-glucose
b-galactose-(1,4)-b-glucose
Galactose-(b14b)-glucose
aglucose-(1,2)-b-fructose
glucose-(a12b)-fructose