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BIOCHEMISTRY | PROTEIN STRUCTURE AND FUNCTION | PROTEIN STRUCTURE | NOTED BY FAKHRY (IG @SFAKHRYM)
v Overview
o The linear consequence of the linked amino acids contains the information necessary to generate a protein molecule with a unique
three-dimensional shape that determines function
• Protein serves in many roles (e
...
, Enzymes, hormone, receptor, antibodies, structural components, transporter of other
compound, and contractile elements in muscle)
o The complexity of protein structure is best analyzed by considering the molecule in terms of four organizational levels: primary,
secondary, tertiary, and quaternary

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BIOCHEMISTRY | PROTEIN STRUCTURE AND FUNCTION | PROTEIN STRUCTURE | NOTED BY FAKHRY (IG @SFAKHRYM)
v PRIMARY STRUCTURE
o It consists of the amino acid sequence along the chain
Understanding the primary structure of protein is important because many genetic diseases result in proteins with
•
abnormal amino acid sequence
• The linear polymer of amino acids contains polarity
...
The polypeptide chain consists of repeating units that make backbone
...

§ When a peptide is named, all amino acid residues have their suffixes (-ine, -an, -ic, or -ate) changed to -yl, with the
exception of the C-terminal amino acid
• Example, a tripeptide composed of an N-terminal valine, a glycine, and a C-terminal leucine is called
valyglycyleucine
The peptide bond has a partial double-bond character, that is, it is shorter than a single bond and is rigid, and planar
•
§ This prevents free rotation around the bond
...


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BIOCHEMISTRY | PROTEIN STRUCTURE AND FUNCTION | PROTEIN STRUCTURE | NOTED BY FAKHRY (IG @SFAKHRYM)

Description: Resonance interactions between electrons in the C=O bond and the C–N bond of the peptide group mean that
there is ‘sharing’ of electrons between these bonds
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The first step in determining the primary structure of a polypeptide is to identify and quantitate its constituent amino acids
• A purified sample of the polypeptide to be analyzed is first hydrolyzed by strong acid at 110° C for 24 hours
§ This treatment cleaves the peptide bonds and releases the individual amino acids, which can be separated by
cation-exchange chromatography
• In this technique, a mixture of amino acids is applied to a column that contains a resin to which a negatively
charged group is tightly attached (if the attached group is positively charged, the column becomes an anionexchange column)
• The aas bind to the column with different affinities, depending on their charges, hydrophobicity, and other
characteristics
• A protein will migrate in an electric field, depending on the sum of its charges at a given pH
• Positively charged proteins are cations and migrate toward the cathode (-)
• Negatively charged proteins are anions and migrate toward the anode (+)
• At the isoelectric pH (pI), the protein does not migrate
Sequencing, is a stepwise process of identifying the specific amino acid at each position in the peptide chain, beginning at the Nterminal end
• Phenylisothiocynate (Edman reagent), is used to label to the amino-terminal residue under mildly alkaline conditions
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Enzymes that hydrolyze peptide bonds are termed peptidases (proteases)
•
§ Note: Exopeptidases cut at the ends of proteins and are divided into aminopeptidases and carboxypeptidases
If the nucleotide sequence can be determined, knowledge of the genetic code allows the sequence of nucleotides to be
translated into the corresponding amino acid sequence of that polypeptide

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BIOCHEMISTRY | PROTEIN STRUCTURE AND FUNCTION | PROTEIN STRUCTURE | NOTED BY FAKHRY (IG @SFAKHRYM)
v SECONDARY STRUCTURE
o The secondary structure includes various types of local conformations in which the atoms of the side chains are not
involved
o Secondary structures are formed by a regular repeating pattern of hydrogen bond formation between backbone atoms
o The α-helix, β-sheet, and β-bend (or, β-turn) are example of secondary structures commonly encountered in proteins
...

§ Hydrogen bonds are individually weak, but collectively stabilize the helix
• Each turn of an α-helix contains 3
...
Thus, aas spaced three or four residues apart in the primary sequence
are spatially close together when folded in the α-helix
• The α-helix is disrupted with the proline residues, in which the ring imposes geometric constraints, and by regions
in which numerous aa residues have charged groups or large, bulky side chains
...

§ Pleating results from successive α-carbons being slightly above or below the plane of the sheet
• The chains may run in the same direction (parallel) or in opposite direction (antiparallel)
• On each β-strand, the R groups of adjacent aas extend in opposite directions, above and below the plane of the β-sheet
§ Note: β-sheet are not flat and have a right-handed curl (twist) when viewed along the polypeptide backbone
Compare to α-helix;
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§ In β-sheets, the β-strands are almost fully extended and the hydrogen bonds between the strands are almost full
extended and the hydrogen bonds between the strands are perpendicular to the polypeptide backbone
§ Contrast, α-helices, the polypeptide is coiled and the hydrogen bonds are parallel to the backbone
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• They are usually found on the surface of protein molecules and often include charged residues
• β-bends are generally composed of four aas
§ One of which may be proline (aa that causes a kink in the polypeptide chain)
§ Glycine (aa with the smallest R group) also frequently found
• β-bends are stabilized by the formation of hydrogen bonds between the first and last residues in the bend
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Supersecondary structures (motifs)
• Globular proteins are constructed by combining secondary structural elements (α-helix, β-sheet, and coils), producing
specific geometric patterns, or motifs
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• As a peptide folds, secondary structures form, driven by the hydrophobic effect (that is, hydrophobic groups come together as
water is released)
Protein denaturation
• It results in the unfolding and disorganization of a protein's secondary and tertiary structures without the hydrolysis of peptide
bonds
• Denaturing agents include heat, urea, organic solvents, strong acids or bases, detergents, and ions of heavy metals (e
...
, lead)
• Under ideal condition, it may be reversible
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Capherones in protein folding
• Most denatured proteins do not resume their native conformations even under favorable environmental conditions
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Coli (GRO ES; DNA J; GRO EL; DNA K)
§ LECTIN chaperones
• Calnexin
• Calreticulin
§ GRP-58 (glucose regulated protein)
§ PDI (Protein disulphide isomerase)
Other types
§ Foldases
• Misfolded protein back to native conformation
§ Disaggregases
• Prevents aggregation
• Prevents prion formation or rescue proteins from aggregated states
§ Holdases
• Protein damage by providing favorable conditions

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BIOCHEMISTRY | PROTEIN STRUCTURE AND FUNCTION | PROTEIN STRUCTURE | NOTED BY FAKHRY (IG @SFAKHRYM)
v QUATERNARY STRUCTURE
o It refers to the spatial arrangement of subunits in a protein that consist of more than one polypeptide chain
o The subunits are joined together by the same types of noncovalent interactions (e
...
, hydrogen bonds, ionic bonds, and
hydrophobic interactions)
o Subunits either may function independently of each other or may work cooperatively, as in hemoglobin
...

o These misfolded proteins are usually tagged and degraded within the cell
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• Amyloid disease
• Amyloids, the accumulation of insoluble fibrous protein aggregates
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§ In AD, the dominant component of the amyloid plaque that accumulate is amyloid β (Aβ)
• It is an extracellular peptide containing 40-42 aa residues
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• The Aβ that is deposited in the brain in AD is derived by enzymic cleavage (by secretases)
§ In PD, amyloid is formed from α-synuclein protein
• Prion (Proteinaceous Infectious Particle) Diseases
• The prion protein (PrP) is the causative agent of transmissible spongioform encephalopathies (TSE), including CreutzfeldtJakob disease in humans, scarpie in sheep, and bovin spongioform encephalopathy in cattle (i
...
, "mad cow" disease)
• The infectious protein is designated of PrPSc (Sc = Scarpie);
§ It is highly resistant to proteolytic degradation and tends to form insoluble aggregates of fibrils
The
noninfectious form of PrPC (C = cellular)
•
§ It is encoded by the same gene as the infectious agent, it is present in normal mammalian brains on the surface of
neurons and glial cells

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