Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 83 Structure Of Proteins Notes. - biochemistry notes pdf, biochemistry mbbs 1st year notes pdf, biochemistry mbbs notes pdf, biochemistry lecture notes, paramedical biochemistry notes, medical biochemistry pdf, biochemistry lecture notes 2022 ppt, biochemistry pdf.
Structure of Proteins
Specific learning objectives
? Structure organization of the Proteins includes:
1) Primary structure (covered in previous lecture)
2) Secondary Structure
3) Tertiary Structure
4) Quaternary Structure
Secondary Structure of Proteins
? Local, regular arrangements of the protein chain are stabilized by hydrogen
bonding.
? Polypeptide chains fold into regular structures such as the alpha () helix, beta ()
sheet, and turns and loops.
? -helices, -strands, and turns are formed by a regular pattern of hydrogen
bonds between the peptide N-H and C=O groups of amino acids (aa) that are near
one another in the linear sequence. Such folded segments are called secondary
structure.
Alpha Helix Is a Coiled Structure Stabilized by Intrachain Hydrogen Bonds
Amino terminus
? The -helix is stabilized by intrachain hydrogen
bonding between the NH and CO groups along
parallel to the helical turn.
? The R groups of each aminoacyl residue in an -
helix face outward.
? Pitch of the -helix: length of one complete turn
along the helix axis and is equal to the product of
the rise (1.5 ?) and the number of amino acid per
turn (3.6), or 5.4 ?.
Fig.4.4 b: Bal -and-stick model of a right handed helix. Lehninger
Principles of Biochemistry
Cont--
Largely -helical protein: Ferritin
? ~75% of the residues in ferritin, a protein
that helps store iron, are in a helices.
? ~25% of all soluble proteins are composed
of a helices connected by loops and turns
of the polypeptide chain.
Fig.2.28: Biochemistry 7th edition by Berg, Tymoczko and Stryer
? Many proteins that span biological
membranes also contain -helices.
Ramachandran diagram for helices
? Right-handed helices are energetical y more
favorable because there is less steric clash between
the side chains and the backbone.
? Amino acids favored: Met, Ala, Leu, Glu, Lys. Amino
acids not-favored: Bulky aromatics, -branched,
those compete with the backbone of H-bond (Ser,
Asp, Asn), and also proline and glycine.
? Polypeptide backbone of an helix is twisted by an
equal amount about each -carbon with a phi ()
angle of -60? and a psi () angle of -47?.
Fig.2.26: Biochemistry 7th edition by Berg, Tymoczko and Stryer
-Sheets Stabilized by Hydrogen Bonding Between Polypeptide Strands
? Distance between adjacent amino acids
along a strand is approximately 3.5 ?.
C
N
C
H
? The side chains are above and below the
O
plane of the strands.
Fig.2.30: Biochemistry 7th edition by Berg, Tymoczko and Stryer
Paral el -sheet
? In the parallel arrangement, for each
aa, the NH group is hydrogen bonded
to the CO group of one aa on the
C
adjacent strand.
R
N
C
H
O
? 1:2 H-bond pattern: 1 a.a bonds with
2 other a.a in an opposing stand.
Fig.2.32: Biochemistry 7th edition by Berg, Tymoczko and Stryer
Antiparal el -sheet
? Adjacent chains in a sheet can run in
opposite directions (antiparallel
sheet) or in the same direction (parallel
C
C
N
sheet).
H
O
? Follow 1:1 H-bond pattern.
? In the antiparallel arrangement, the NH
group and the CO group of each aa are
respectively hydrogen bonded to the
Fig.2.31: Biochemistry 7th edition by Berg, Tymoczko and Stryer
CO group and the NH group of a
partner on the adjacent chain.
Ramachandran diagram for Beta strands
? Ramachandran angles occupy the upper quadrant
(=-135? and =+135?).
? The pink area shows the sterically allowed
conformations of extended, -strand like
structures.
? -strand is extended rather than being tightly
coiled as in the -helix.
Fig.2.29: Biochemistry 7th edition by Berg, Tymoczko and Stryer
Protein rich in -sheet
? Fatty acid-binding proteins (FABP),
important for lipid metabolism, are
built almost entirely from -sheets.
Fig.2.35: Biochemistry 7th edition by Berg, Tymoczko and Stryer
Reverse Turns
? In compact globular proteins, a polypeptide
often makes a sharp turn.
? They cause packing and make it possible for
the molecule to become globular.
? Turns connect helical twists and sheets.
N
H
C
O
? The structure is a 180? turn involving four aa
residues, with the CO of the residue i forming a
hydrogen bond with the NH of the residue i+3.
Fig.3.42: Biochemistry 7th edition by Berg, Tymoczko and Stryer
Cont--
? Loops are responsible for chain reversals and
overal shape.
? Turns and loops invariably lie on the surfaces of
proteins and participate in the recognition role
of proteins, such as the recognition of specific
antigens by antibodies.
? Ex. part of antibody molecule has surface loops
(shown in red) that mediate interactions with
other molecules.
Fig.3.43: Biochemistry 7th edition by Berg, Tymoczko and Stryer
Special types of helices are present in the two proteins
1. -keratin is an elongated -helix. Pairs of
these helices are interwound in a left-handed
sense to form two-chain coiled coils.
? These combine in higher-order structures
called protofilaments and protofibrils.
? About four protofibrils--32 strands of -
keratin altogether--combine to form an
intermediate filament.
? Contribute to the cell cytoskeleton (internal
scaffolding in a cell), and the muscle proteins
Fig.4.11: Biochemistry 7th edition by Berg, Tymoczko and Stryer
myosin and tropomyosin.
Cont--
2. Col agen is the main fibrous component of skin,
bone, tendon, cartilage, and teeth.
? Glycine appears at every third residue in the
amino acid sequence.
? Hydrogen bonds within a strand are absent.
Helix is stabilized by steric repulsion of the
pyrrolidine rings of the proline and
hydroxyproline residues.
Fig.2.40: Biochemistry 7th edition by Berg, Tymoczko and Stryer
Cont--
? Importance of the positioning of glycine inside the triple helix is il ustrated in
osteogenesis imperfecta. In this condition, other amino acids replace the internal
glycine residue.
? The -OH groups of hydroxyproline residues participate in hydrogen bonding, and
the absence of the -OH groups results in the disease scurvy.
Tertiary Structure of Proteins
Tertiary Structure: Water-Soluble Proteins Fold Into Compact Structures with Nonpolar Cores
? The tertiary structure of a protein is its 3-
D arrangement; that is, the folding of its
2?structural elements, together with the
spatial dispositions of its side chains.
? Ex. myoglobin carried out by John
Kendrew and his colleagues in the 1950s.
? Myoglobin, the oxygen carrier in muscle.
It functions both to store oxygen and to
facilitate oxygen diffusion in rapidly
Fig.3.44 b: Biochemistry 7th edition by Berg, Tymoczko and Stryer
contracting muscle tissue.
? Capacity of myoglobin to bind oxygen depends on the presence of heme, a non-
polypeptide prosthetic group consisting of protoporphyrin IX and a central iron
atom.
? The interior consists of nonpolar residues such as leucine, valine, methionine,
and phenylalanine.
? The only polar residues inside are two histidine residues, play critical roles in
binding iron and oxygen. The outside of myoglobin, consists of both polar and
nonpolar residues.
? Principles of the Protein structure:
1. Hydrophobic amino acid side chains located interior of the protein and
hydrophilic side chains are located on the exterior of the protein.
2. Structure: Devoid of symmetry (globular).
3. Tightly packed.
4. Tertiary structure also include disulfide bonds.
Cont---
5. Polypeptide chains folded into a spherical or globular shape. Globular proteins
are stabilized by all weak interactions:
a) Hydrogen bonds
b) Hydrophobic interactions
c) Ionic interactions: Negatively charged groups, such as the carboxylate group (?
COO?) in the side chain of aspartate or glutamate, can interact with positively
charged groups such as the amino group (? NH3+) in the side chain of lysine.
d) Vander wal 's forces: Contribute to both the packing of atoms in proteins as well
as the space between atoms.
Cont---
6. Tertiary structure can be sub-divided into domains:
? Part of protein sequence and structure that can evolve, function, and exist independently
of the rest of the protein chain. , ex. ligand binding domain, membrane spanning domain.
? Protein domain is a conserved part of a given protein sequence and tertiary structure
that can evolve, function and exist independently of the rest of the protein chain.
? Independently folded portion of the protein linked by helical hinges.
? Evolutionary conserved structure common in many proteins.
Cont--
? Many proteins consist of several structural
domain. Ex. Protein pyruvate kinase show
three domains:
a) It contains an all- nucleotide binding
domain (in blue).
b) /-substrate binding domain (in grey).
c) /-regulatory domain (in green) connected
by several polypeptide linkers.
Wikipedia
Quaternary Structure of Proteins
Quaternary Structure: Polypeptide Chains Can Assemble
Into Multi-subunit Structures
? This level of protein structure applies only to those proteins that consist of more
than one polypeptide chain, termed subunits.
? Quaternary structure implies the non-covalent interaction that stabilise the
folded polypeptides leads to multisubunit proteins.
Cont--
? Multisubunit proteins can have a number of identical (homomeric) or non-
identical (heteromeric) subunits.
? The simplest multisubunit proteins are homodimers ? two identical polypeptide
chains that are independently folded but held together by non-covalent
interactions.
Cont--
? Example. Hemoglobin (Hb), oxygen
carrying protein in blood contains
four polypeptide chains and four
heme prosthetic groups, in which
the iron atoms are in the ferrous
(Fe2+) state.
? The protein portion, called globin,
consists of two -chains and two
-chains.
Fig.3.49: Biochemistry 7th edition by Berg, Tymoczko and Stryer
Cont--
? Subunits of Hb are arranged in symmetric pairs, each pair having one and one
subunit.
? Hb exists as an
2 2 tetramer. Subtle changes in the arrangement of subunits
within the Hb molecule allow it to carry oxygen from the lungs to tissues with
great efficiency.
Summary
? The gene-encoded primary structure of a polypeptide is the sequence of its
amino acids.
? Secondary structure refers to stable arrangements of amino acid residues giving
rise to recurring structural patterns.
? Folding of polypeptides into hydrogen-bonded motifs such as the helix, the -
pleated sheet, bends, and loops.
? Tertiary structure is the complete three-dimensional structure of a polypeptide
chain.
? When a protein has two or more polypeptide subunits, their arrangement in
space is referred to as quaternary structure
Interaction with students
? Distributed subtopics of class to students for participate in group
discussion in next class.
Reference Books
1) Harper 's Il ustrated Biochemistry-30th edition
2) Biochemistry. 4th edition. Donald Voet and Judith G. Voet.
3) Biochemistry 7th edition by Jeremy M. Berg, John L. Tymoczko and Lubert Stryer
4) Lehninger Principles of Biochemistry
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Thank you
This post was last modified on 05 April 2022