Download MBBS Biochemistry PPT 83 Structure Of Proteins Lecture Notes

--- Content provided by​ FirstRanker.com ---

? Structure organization of the Proteins includes:
1) Primary structure (covered in previous lecture)

2) Secondary Structure

--- Content provided by​ FirstRanker.com ---

3) Tertiary Structure

4) Quaternary Structure
Secondary Structure of Proteins

--- Content provided by‍ FirstRanker.com ---

? Local, regular arrangements of the protein chain are stabilized by hydrogen

bonding.

? Polypeptide chains fold into regular structures such as the alpha () helix, beta ()

--- Content provided by‍ FirstRanker.com ---

sheet, and turns and loops.

? -helices, -strands, and turns are formed by a regular pattern of hydrogen

--- Content provided by‌ FirstRanker.com ---

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.

--- Content provided by‌ FirstRanker.com ---

Alpha Helix Is a Coiled Structure Stabilized by Intrachain Hydrogen Bonds

Amino terminus

? The -helix is stabilized by intrachain hydrogen

--- Content provided by⁠ FirstRanker.com ---

bonding between the NH and CO groups along

parallel to the helical turn.

--- Content provided by⁠ FirstRanker.com ---

? The R groups of each aminoacyl residue in an -

helix face outward.

? Pitch of the -helix: length of one complete turn

--- Content provided by‍ FirstRanker.com ---

along the helix axis and is equal to the product of

the rise (1.5 ?) and the number of amino acid per

--- Content provided by‌ FirstRanker.com ---

turn (3.6), or 5.4 ?.

Fig.4.4 b: Bal -and-stick model of a right handed helix. Lehninger

Principles of Biochemistry

--- Content provided by FirstRanker.com ---

Cont--

Largely -helical protein: Ferritin

--- Content provided by‍ FirstRanker.com ---

? ~75% of the residues in ferritin, a protein

that helps store iron, are in a helices.

? ~25% of all soluble proteins are composed

--- Content provided by‍ FirstRanker.com ---

of a helices connected by loops and turns

of the polypeptide chain.

--- Content provided by‌ FirstRanker.com ---

Fig.2.28: Biochemistry 7th edition by Berg, Tymoczko and Stryer

? Many proteins that span biological

membranes also contain -helices.

--- Content provided by‌ FirstRanker.com ---

Ramachandran diagram for helices

? Right-handed helices are energetical y more

favorable because there is less steric clash between

--- Content provided by​ FirstRanker.com ---

the side chains and the backbone.

? Amino acids favored: Met, Ala, Leu, Glu, Lys. Amino

--- Content provided by FirstRanker.com ---

acids not-favored: Bulky aromatics, -branched,

those compete with the backbone of H-bond (Ser,

Asp, Asn), and also proline and glycine.

--- Content provided by​ FirstRanker.com ---

? Polypeptide backbone of an helix is twisted by an

equal amount about each -carbon with a phi ()

--- Content provided by​ FirstRanker.com ---

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

--- Content provided by​ FirstRanker.com ---

? Distance between adjacent amino acids

along a strand is approximately 3.5 ?.

--- Content provided by⁠ FirstRanker.com ---

C

N

C

--- Content provided by​ FirstRanker.com ---

H

? The side chains are above and below the

--- Content provided by​ FirstRanker.com ---

O

plane of the strands.

Fig.2.30: Biochemistry 7th edition by Berg, Tymoczko and Stryer

--- Content provided by​ FirstRanker.com ---

Paral el -sheet

? In the parallel arrangement, for each

aa, the NH group is hydrogen bonded

--- Content provided by‌ FirstRanker.com ---

to the CO group of one aa on the

C

--- Content provided by‌ FirstRanker.com ---

adjacent strand.

R

N

--- Content provided by‍ FirstRanker.com ---

C

H

--- Content provided by‍ FirstRanker.com ---

O

? 1:2 H-bond pattern: 1 a.a bonds with

2 other a.a in an opposing stand.

--- Content provided by​ FirstRanker.com ---

Fig.2.32: Biochemistry 7th edition by Berg, Tymoczko and Stryer

Antiparal el -sheet

--- Content provided by‍ FirstRanker.com ---

? Adjacent chains in a sheet can run in

opposite directions (antiparallel

sheet) or in the same direction (parallel

--- Content provided by​ FirstRanker.com ---

C

C

--- Content provided by‍ FirstRanker.com ---

N

sheet).

H

--- Content provided by⁠ FirstRanker.com ---

O

? Follow 1:1 H-bond pattern.

--- Content provided by FirstRanker.com ---

? In the antiparallel arrangement, the NH

group and the CO group of each aa are

respectively hydrogen bonded to the

--- Content provided by FirstRanker.com ---

Fig.2.31: Biochemistry 7th edition by Berg, Tymoczko and Stryer

CO group and the NH group of a

--- Content provided by​ FirstRanker.com ---

partner on the adjacent chain.
Ramachandran diagram for Beta strands

? Ramachandran angles occupy the upper quadrant

--- Content provided by FirstRanker.com ---

(=-135? and =+135?).

? The pink area shows the sterically allowed

conformations of extended, -strand like

--- Content provided by‍ FirstRanker.com ---

structures.

? -strand is extended rather than being tightly

--- Content provided by FirstRanker.com ---

coiled as in the -helix.

Fig.2.29: Biochemistry 7th edition by Berg, Tymoczko and Stryer

Protein rich in -sheet

--- Content provided by FirstRanker.com ---

? Fatty acid-binding proteins (FABP),

important for lipid metabolism, are

--- Content provided by‍ FirstRanker.com ---

built almost entirely from -sheets.

Fig.2.35: Biochemistry 7th edition by Berg, Tymoczko and Stryer
Reverse Turns

--- Content provided by‌ FirstRanker.com ---

? In compact globular proteins, a polypeptide

often makes a sharp turn.

? They cause packing and make it possible for

--- Content provided by​ FirstRanker.com ---

the molecule to become globular.

? Turns connect helical twists and sheets.

--- Content provided by⁠ FirstRanker.com ---

N

H

C

--- Content provided by​ FirstRanker.com ---

O

? The structure is a 180? turn involving four aa

--- Content provided by‍ FirstRanker.com ---

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

--- Content provided by FirstRanker.com ---

Cont--

? Loops are responsible for chain reversals and

--- Content provided by‌ FirstRanker.com ---

overal shape.

? Turns and loops invariably lie on the surfaces of

proteins and participate in the recognition role

--- Content provided by FirstRanker.com ---

of proteins, such as the recognition of specific

antigens by antibodies.

--- Content provided by​ FirstRanker.com ---

? Ex. part of antibody molecule has surface loops

(shown in red) that mediate interactions with

other molecules.

--- Content provided by FirstRanker.com ---

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

--- Content provided by⁠ FirstRanker.com ---

these helices are interwound in a left-handed

sense to form two-chain coiled coils.

--- Content provided by​ FirstRanker.com ---

? These combine in higher-order structures

called protofilaments and protofibrils.

? About four protofibrils--32 strands of -

--- Content provided by⁠ FirstRanker.com ---

keratin altogether--combine to form an

intermediate filament.

--- Content provided by‍ FirstRanker.com ---

? 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

--- Content provided by‍ FirstRanker.com ---

myosin and tropomyosin.

Cont--

--- Content provided by‌ FirstRanker.com ---

2. Col agen is the main fibrous component of skin,

bone, tendon, cartilage, and teeth.

? Glycine appears at every third residue in the

--- Content provided by FirstRanker.com ---

amino acid sequence.

? Hydrogen bonds within a strand are absent.

--- Content provided by FirstRanker.com ---

Helix is stabilized by steric repulsion of the

pyrrolidine rings of the proline and

hydroxyproline residues.

--- Content provided by FirstRanker.com ---

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

--- Content provided by​ FirstRanker.com ---

osteogenesis imperfecta. In this condition, other amino acids replace the internal

glycine residue.

--- Content provided by FirstRanker.com ---

? 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

--- Content provided by‌ FirstRanker.com ---

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

--- Content provided by FirstRanker.com ---

2?structural elements, together with the

spatial dispositions of its side chains.

--- Content provided by‍ FirstRanker.com ---

? Ex. myoglobin carried out by John

Kendrew and his colleagues in the 1950s.

? Myoglobin, the oxygen carrier in muscle.

--- Content provided by⁠ FirstRanker.com ---

It functions both to store oxygen and to

facilitate oxygen diffusion in rapidly

--- Content provided by‌ FirstRanker.com ---

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-

--- Content provided by‌ FirstRanker.com ---

polypeptide prosthetic group consisting of protoporphyrin IX and a central iron

atom.

--- Content provided by‌ FirstRanker.com ---

? 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

--- Content provided by⁠ FirstRanker.com ---

binding iron and oxygen. The outside of myoglobin, consists of both polar and

nonpolar residues.
? Principles of the Protein structure:

--- Content provided by‌ FirstRanker.com ---

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).

--- Content provided by‍ FirstRanker.com ---

3. Tightly packed.

4. Tertiary structure also include disulfide bonds.

--- Content provided by​ FirstRanker.com ---

Cont---

5. Polypeptide chains folded into a spherical or globular shape. Globular proteins

are stabilized by all weak interactions:

--- Content provided by​ FirstRanker.com ---

a) Hydrogen bonds
b) Hydrophobic interactions
c) Ionic interactions: Negatively charged groups, such as the carboxylate group (?

--- Content provided by​ FirstRanker.com ---

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

--- Content provided by​ FirstRanker.com ---

as the space between atoms.
Cont---

6. Tertiary structure can be sub-divided into domains:

--- Content provided by⁠ FirstRanker.com ---

? 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

--- Content provided by FirstRanker.com ---

that can evolve, function and exist independently of the rest of the protein chain.

? Independently folded portion of the protein linked by helical hinges.

--- Content provided by‌ FirstRanker.com ---

? Evolutionary conserved structure common in many proteins.

Cont--

? Many proteins consist of several structural

--- Content provided by⁠ FirstRanker.com ---

domain. Ex. Protein pyruvate kinase show

three domains:

--- Content provided by⁠ FirstRanker.com ---

a) It contains an all- nucleotide binding

domain (in blue).

b) /-substrate binding domain (in grey).

--- Content provided by⁠ FirstRanker.com ---

c) /-regulatory domain (in green) connected

by several polypeptide linkers.

--- Content provided by⁠ FirstRanker.com ---

Wikipedia
Quaternary Structure of Proteins

Quaternary Structure: Polypeptide Chains Can Assemble

--- Content provided by​ FirstRanker.com ---

Into Multi-subunit Structures

? This level of protein structure applies only to those proteins that consist of more

than one polypeptide chain, termed subunits.

--- Content provided by‍ FirstRanker.com ---

? Quaternary structure implies the non-covalent interaction that stabilise the

folded polypeptides leads to multisubunit proteins.
Cont--

--- Content provided by⁠ FirstRanker.com ---

? Multisubunit proteins can have a number of identical (homomeric) or non-

identical (heteromeric) subunits.

--- Content provided by⁠ FirstRanker.com ---

? The simplest multisubunit proteins are homodimers ? two identical polypeptide

chains that are independently folded but held together by non-covalent

interactions.

--- Content provided by⁠ FirstRanker.com ---

Cont--

? Example. Hemoglobin (Hb), oxygen

--- Content provided by‌ FirstRanker.com ---

carrying protein in blood contains

four polypeptide chains and four

heme prosthetic groups, in which

--- Content provided by‍ FirstRanker.com ---

the iron atoms are in the ferrous

(Fe2+) state.

--- Content provided by​ FirstRanker.com ---

? The protein portion, called globin,

consists of two -chains and two

-chains.

--- Content provided by⁠ FirstRanker.com ---

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

--- Content provided by‌ FirstRanker.com ---

subunit.

? Hb exists as an

--- Content provided by‌ FirstRanker.com ---

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.

--- Content provided by‍ FirstRanker.com ---

Summary

? The gene-encoded primary structure of a polypeptide is the sequence of its

--- Content provided by FirstRanker.com ---

amino acids.

? Secondary structure refers to stable arrangements of amino acid residues giving

rise to recurring structural patterns.

--- Content provided by‌ FirstRanker.com ---

? 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

--- Content provided by‍ FirstRanker.com ---

chain.

? When a protein has two or more polypeptide subunits, their arrangement in

--- Content provided by FirstRanker.com ---

space is referred to as quaternary structure

Interaction with students

? Distributed subtopics of class to students for participate in group

--- Content provided by FirstRanker.com ---

discussion in next class.
Reference Books

1) Harper 's Il ustrated Biochemistry-30th edition

--- Content provided by FirstRanker.com ---

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

33

--- Content provided by‌ FirstRanker.com ---

Thank you