Transcript structure-peptidebond-text

CHMI 2227E
Biochemistry I
Proteins:
-Levels
of Protein Structure
-Conformation of Peptide Group
CHMI 2227 - E.R. Gauthier, Ph.D.
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Proteins: Levels of Protein
Structure

Individual proteins
molecules can be
described by up to
four levels of
structures
 Primary
Structure
 Secondary
Structure
 Tertiary Structure
 Quaternary
Structure
http://macromolecules.ucsf.edu/Lectures/Tanja%20Macromol_forces%202006.pdf
CHMI 2227 - E.R. Gauthier, Ph.D.
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Primary Structure

Sequence of amino acids in the
polypeptide chain;

Primary structure is a complete
description of all the covalent
bonding in a polypeptide chain or
protein;

In some proteins, the linear
polypeptide chain is cross-linked


http://www.fiu.edu/~bch3033/Handouts/Lh4Ch04Prot.pdf
Disulfide bonds
However, the primary structure does
not indicate the position of the
amino acids in space
CHMI 2227 - E.R. Gauthier, Ph.D.
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Secondary Structure

It is the ordered arrangement or
conformation of amino acids in
localized regions of a polypeptide
or protein molecule;

Hydrogen bonding plays an
important role in stabilizing these
folding patterns;

The two main secondary
structures are the alpha helix and
beta-pleated sheet
http://www.fiu.edu/~bch3033/Handouts/Lh4Ch04Prot.pdf
CHMI 2227 - E.R. Gauthier, Ph.D.
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Tertiary Structure

It is the combination
of all of the secondary
structures adopted by
the different local
regions of the protein;

It is the 3D
arrangement of the
atoms within a single
polypeptide chain;
http://www.fiu.edu/~bch3033/Handouts/Lh4Ch04Prot.pdf
CHMI 2227 - E.R. Gauthier, Ph.D.
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Quaternary Structure

It is used to describe proteins composed
of multiple subunits (multiple
polypeptide molecules each called a
monomer);

The subunits can be identical or
different;

Most proteins with a molecular weight
greater than 50 000 Da consist of two http://www.fiu.edu/~bch3033/Handouts/Lh4Ch04Prot.pdf
or
more noncovalently-linked monomers;

The arrangement of the monomers in the
3D protein is the quaternary structure
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Proteins

The formation of higher levels of
organization (2°, 3° and 4°) is done is a
very precise way;

A protein usually adopts a single tertiary
structure: this is also called the native
conformation of the protein

For proper folding, weak non-covalent
forces are required
CHMI 2227 - E.R. Gauthier, Ph.D.
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Secondary Structure of Proteins

The elucidation of the secondary structures of
proteins was possible only after understanding
the geometry of the peptide bond
http://employees.csbsju.edu/hjakubowski/classes/ch331/protstructure/olunderstandconfo.html

The peptide bond is essentially planar
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Conformation of the Peptide Group

If the peptide bond
is planar, therefore,
the two atoms
involved in the
peptide bond along
with the four
substituents
(carbonyl oxygen
atom, the amide
hydrogen atom,
and the two
adjacent α-carbon
atoms) lie in the
same plane
Peptide Group
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Peptide bond has resonance structures!
Peptide bond is shown as
single C-N bond
Peptide bond is shown as
a double bond
Actual structure is best represented as a hybrid of the 2
resonance structures in which electrons are delocalized
over the carbonyl oxygen, the carbonyl carbon and the
amide nitrogen. Rotation around the C-N bond is
restricted due to the double bond nature of the
resonance hybrid form
Note: Peptide bond is polar! The oxygen and nitrogen
atoms have partial negative and positive charges,
respectively
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Conformation of the peptide group

Peptide bond has a double bond nature,
therefore, the conformation of the peptide group
is restricted to one of two possible
conformations, either Trans or Cis
Figure 3.25 Biochemistry 2001, Fifth Edition
CHMI 2227 - E.R. Gauthier, Ph.D.
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Cis conformation of the peptide
group

The two α-carbons
atoms are on the same
side of the peptide bond
and are closer together;
O
Cα

The cis conformation is
less favorable than the
extended trans
conformation because of
steric interference
between the side chains
CHMI 2227 - E.R. Gauthier, Ph.D.
H
C
R1
N
Cα
R2
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Trans conformation of the peptide
group


The two α-carbons atoms are
on opposite sides of the
peptide bond and at opposite
corners of the rectangle formed
by the planar peptide group;
R1
H
C
Cα
Consequently, nearly all
peptide groups in proteins are
in the trans conformation
CHMI 2227 - E.R. Gauthier, Ph.D.
N
Cα
O
R2
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Exceptions to the rule!
Figure 3.26 Biochemistry 2001, Fifth Edition

Cis conformation does exist;

Most common is the X-Pro linkage

10% of the proline residues in protein follow a cis peptide bond

These bonds show less preference for the trans conformation because
the nitrogen of proline is bonded to two tetrahedral carbon atoms limiting
the steric differences between trans and cis forms
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Psi and Phi Angles


In contrast to the peptide bond, the bonds between the
amino group and the α-carbon atom and between the αcarbon atom and the carbonyl group are pure single
bonds
The rotation around N-Cα bond of the peptide group is
designated Φ (phi) and that around Cα-C is designated
Ψ (psi)
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Psi and Phi Angles

Each of these angles
is defined by the
relative position of four
atoms of the
backbone;

Clockwise angles are
positive and
counterclockwise
angles are negative
with each having a
180° sweep;
Peptide Bond

Each rotation angles
range from -180° to
+180°
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Psi and Phi Angles

The two adjacent rigid peptide units may rotate
about these bonds taking on various
orientations;

These rotations are restricted by steric
interference limiting the permissible angles
 Interference
between main-chain and side-chain
atoms of adjacent residues
 Interference between carbonyl oxygens on adjacent
residues
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Animation of Phi rotation
Phi rotation
http://employees.csbsju.edu/hjakubowski/classes/ch331/protstructure/olunderstandconfo.html
CHMI 2227 - E.R. Gauthier, Ph.D.
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Animation of Psi rotation
Psi rotation
http://employees.csbsju.edu/hjakubowski/classes/ch331/protstructure/olunderstandconfo.html
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Ramachandran Plot


Biophysicist G. N.
Ramachandran
constructed a space filling
model of peptides and
made calculations to
determine which values
of Φ and Ψ are sterically
permitted in a
polypeptide chain
Permissible angles are
shown as colored regions
in the Ramachandran
plots of Φ vs Ψ
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Ramachandran Plot
The conformations of several types of
ideal secondary structures fall within the
shaded areas
 Blank areas are nonpermissible angles
due to steric hindrance

Figure 3.28 Biochemistry 2001, Fifth Edition
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