Overview
•  Secondary structure: the conformation of the
peptide backbone
• 
• 
• 
• 
•  The peptide bond, steric implications
•  Steric hindrance and sterically allowed
conformations. Ramachandran diagrams
Side chain conformations
Backbone hydrogen bonding
Recurring regular structures of the backbone
•  Alfa helix, other helices
•  Beta sheet
Reccuring irregular structures: Turns
The peptide bond
Delocalization; double bond character:
Resonance structures:
O
C!
Geometry of the trans peptide bond
N
H
C!
O
C!
N
C!
or
O
Shorter than ordinary
C-N bond
+
H
!"
N
H
!+
Consequences:
• Very limited rotation around C-N-bond;
O,C,N,H in one plane
• Cis-trans isomerism
• Permanent dipole; polar
+
Page 1
cis- och trans peptides
Cis, rare (cis-prolin [X-cisPro-])
Trans, common
HR
H R
R H
H
N
N
O
O
H
R H
Proline
Trans-proline
Cis-proline
Page 2
Two conformational degrees of freedom for
each residue
For each residue, the
backbone conformation
can be specified by the
torsion angles φ and ψ
C
Res. nr. i
Oi-1
i-1
Cβi R
Cαi
φ
Ni+1
ψ
Ni
C
i
Hi
Oi
Oi
φ
C
Ni
i
Cαi C
φ=0 when
Cαi-C i
trans
to Ni-Hi
i
Ni
Ψ
ψ=0 when
Cαi-Ni
trans
to C i-Oi
Hi
Ni+1
Petsko&Ringe fig. 1.9
Steric hindrance and van der Waals
distances
Observed distances (Å)
Repulsion between
electron clouds
proportional to (1/r)12;
atoms can be regarded as
hard spheres
Contact
H .. H
H .. O
H .. N
H .. C
O .. O
O .. N
O .. C
N .. N
N .. C
C .. C
Normal
2.0
2.4
2.4
2.4
2.7
2.7
2.8
2.7
2.9
3.0
Extreme
1.9
2.2
2.2
2.2
2.6
2.6
2.7
2.6
2.8
2.9
Schultz & Schirmer: Principles
of Protein Structure
Page 3
Steric hindrance and allowed conformation
(φ,ψ) for glycine residue
φ=0, ψ=80
φ
φ=0, ψ=180
φ=0, ψ=90
ψ
φ=0, ψ=0
φ=-180, ψ=0
φ=-90, ψ=0
Shultz & Schirmer, Principles of protein
structure
A β-carbon imposes further restrictions
φ
ψ
Sidechain in all
amino acids except
glycine
φ about 130; On-1 - Cβ
ψ about -100; Nn-1,Hn-1 - Cβ
φ
Efter Shultz & Schirmer, Principles of
protein structure
Page 4
ψ
Energy as function of geometry-a more detailed
calculation
Potential energy diagram for alanine residie (geometry of
peptide bond and bond legnths fixed; Shultz och Schirmer:
Principles of Protein Structure)
> 0 kcal/mol
-1 - 0 kcal/mol
-2 - -1 kcal mol
-3 - -2 kcal/mol
-4 - -3kcal/mol
Bridge region;
Steric repulsion between
Ni och Hi+1 compensated
by favourable dipoledipole interaction
φ=-90, ψ=0
δ+
δ-
δ+
δ-
Efter Shultz & Schirmer, Principles of
protein structure
Experimental φ and ψ: Ramachandran diagrams
Ramachandrandiagram for 13
proteins (2500 residues)
•  Ca 5 % of all residues with βcarbon (≠Gly) in forbidden areas
•  Realistic calculations need to take
into account •  Peptide bond torsion: (|Ω| <
12o increses energy < 1 kcal/
mol)
•  Small variations of bond
angles and lengths are OK
energywise
Efter Shultz och Schirmer:
Principles of Protein Structure
Page 5
Conformational preferences of residues as
Ramachandran diagrams
Examples
Hovmöller et al; www.fos.su.se/~svenh/
Description of side chain conformation with
torsional angles
Denoted χ1, χ2....
χ1i
χ2i
Från Schultz & Schirmer:
Principles of Protein Structure
Page 6
Nomenclature for side chains
Figur av Jon Cooper, PPS
Side chain conformations
χ1
Most frequent ;
Cγ opposite
carbonyl carbon
Second most
common (not Val, Ile)
Cα
χ2
Oftast som χ1
Med Cγ sp2 (Phe, Tyr, Trp,
His...) ± 90 grader (?)
H
Uncommon;
however Ser, Thr
(H-bond Oγbackbone)
Cβ
Figur av Jon Cooper, PPS
H
Page 7
Exemples of observed rotamerer preferences
Val
Ile
His
χ1
χ1
χ2
χ2
Repetition of φ and ψ produces helixes
Parameters to describe a helix
•  Units per turn, n
(positive for right-anded;
negative for left-handed
•  Distance along axis per turn,
p (pitch)
p
•  Radius
d
Alternatives
• 
Angle between units; 360/n
• 
Distance along axis per
unit , d=p/n
r
Page 8
Helix structures
p
p=0
n=5
n=4
p
p
p
n=3
n=2
not
chiral
n=-3
n does not need to be an integer except when p=0
Figur av Irving Geis, från Voet och voet, Biochemistry
Torsional angles and helix parameters
Helix parameters d and n
for helixes obtained by
assigning same torsional
angles ψ and φ to
residues in a polypeptide
chain
ψ
d
n
φ
Page 9
From Shultz och Schirmer:
Principles of Protein Structure
Secondary structure
•  Structure that can be described using only
the backbone torsional angles φ och ψ
•  No steric hindrance involving backbone or Cβ
•  Backbone carbonyl and amides involved in
hydrogen bonding to backbone
Hydrogen bonding possibilitites
i!
i+1
i+2
27 ribbon
i+3
310 helix
i+4
α helix
i+5
π helix
Figur av Irving Geis, hämtad ur Matthews & van Holde, Biochemistry
Page 10
Helix structures
(Helical parameters for various secondary structures)
Table 5-1. Linear Groups Formed by Polypeptide Chains (Schultz och Schirmer,
Principles of Protein Structure)
Linear group
Observed
Residues per
Rise per
turn n and
chirality
residue
d (A)
Radius of
helix r
(A)
Planar parallel sheet
Rare
±2.0
3.2
1 . 1
Planar antiparallel sheet
Rare
±2.0
3.4
0.9
Twisted parallel or
Abundant
- 2.3
3.3
1.0
antiparallel sheet
3 1 0-Helix
Small pieces
+ 3.0
2.0
1.9
a(R)-Helix (right-handed)
Abundant
+ 3.6
1.5
2.3
a(L)-Helix (left-handed)
Hypothetical
- 3.6
1.5
2.3
IT-Helix
Hypothetical
+ 4.3
1.1
2.8
Collagen-helix
In fibers
- 3.3
2.9
1.6
See also Petsko&Ringe fig. 1.14
Alpha helix
From
top
Spacefilling
model (CPK)
Stick model:
Hydrogen bonding
i+4
i+3
i+4
i+2
i+2
i+1
i
i+1
i
• Common; accounts for
about 35 % of all
structure
• Suitable radius for good
van der Waals
interaction
• Side chains point away
from each other; minimal
steric hindrance
Pesko&Ringe fig 1.13
Page 11
3.10 helix
Hydrogen bonding
Top view
CPK-model
• Rare ca. 3 % short
fragments (1-3 hydrogen
bonds)
• (φ,ψ)=(-74,-4), borderline
• Radius smaller than van der
Waals distance
• Sidechains not will spaced
evenly
Dipole moment
Addition of permanent dipole moments of peptide bonds produces net
dipole moment for alpha helixes; ( about +0.5 i C-terminus och -0.5 i Nterminus)
Some preference for negatively charged sidechains
at the N-terminus and for positively charged side
chains at the C-terminus. Phosphate binding oftan
at N-terminus of alpha helix
Figur av Doc. Kurt Berndt, Karolinska Institute;
se Bränden& Tooze s. 16
Page 12
Amphiphatic alpha helixes
Perodicity in sequence (period ov 3-4
residues) can produce) amphiphilic
helix.
Strongly amphiphilic alpha heices can be
recognized by hydrophobic moment:
Helical wheel diagram
Non<polar
N
R
Take the hydrophobicity of each residue
as the length of a vector directed from the
helix as the sidechain. The length of the
vector sum is called hyrdophobic moment
Polar
D
Charged
F
C-term
S
I
D
L
N-term
G
L
G
Alcohol dehydrogenase:
Ile-Gln-Asp-Gly-Phe-Asp-Leu-Leu-Arg-Ser-Gly
Amphiphilic alpha helix in
mellitin (bee venom). Efter
Gennis, Biomembranes
Petsko&Ringe fig. 1.15
β-structure
• About 2 residues /turn; planar
• One β-strand:
•  Always together with other strands; carbonyl oxygens
and amide nitrogens hydrogen bonded
Page 13
Association av β-strands with hydrogen bonds
produces a planar structure , β pleated sheet
(β-sheet)
Almost ideal βstructurer från
glutathion
reductase
From the side
β-strands can be parallel or antiparallel
Parallell beta structure
!
HN!
R!
O!
HN!
R!
R!
O!
HN!
R!
O!
R!
O!
HN!
R!
R!
O!
HN!
R!
O!
O!
HN!
R!
O!
HN!
R!
R!
R!
R!
O!
HN!
R!
R!
R!
R!
HN!
O!
R!
HN!
R!
O!
R!
O!
HN!
R!
HN!
R!
O!
R!
O!
HN!
HN!
R!
O!
HN!
R!
O!
HN!
O!
R!
O!
R!
NH!
O!
HN!
Petsko&Ringe fig. 1.17
Page 14
R!
O!
R!
NH!
NH!
R!
O!
O!
NH!
NH!
NH!
R!
O!
O!
NH!
NH!
NH!
NH!
NH!
O!
NH!
O!
HN!
R!
O!
O!
O!
O!
HN!
HN!
NH!
R!
R!
NH!
R!
R!
NH!
O!
HN!
!
HN!
O!
O!
O!
NH!
R!
NH!
NH!
NH!
O!
NH!
R!
O!
O!
HN!
O!
NH!
NH!
NH!
R!
O!
O!
NH!
HN!
Antiparallell beta structure
R!
Most β-strands are twisted
n ≈ -2.3
Strands will
form an angle of
about 25
degrees
β-sheet becomes
twisted;
propellerlike
structure
Schultz och schirmer, Principles of Protein Structure
Twisted β-structure
( thioredoxin)
From top
From side
Page 15
Turns
- Connections between antiparallel beta strands
-mostly short (2-5 residues)
Type I turn
!
(Note that turn
nomenclature is not
consistent)
1,4
2
G
3
Page 16
Type II turn
1,4
3
2
Liten bit 3.10-helix
Petsko&Ringe fig 1.12
Gamma turn: hydrogen bond from O(i) till H(i+2)
Som 2.7 ribbon i vätebindningsöversikten. Endast en rest
som inte ingår i förbundna betasträngar.
stereoisomerer
Figurer av Kurt Berndt, Karlinska Institutet (PPS),
Page 17
Conformational preferences for residues in turn
region
Gly (>50 % of turn residues)
Page 18
Other