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Concepts of biochemistry
Biochem. 700
Protein
Definition:
Proteins are complex biomolecules (organic compounds) composed of many
amino acids linked together through peptide bonds.
Peptide bond????
Peptide bond
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• This allows Hydrogen bonds to form between peptide bonds in different parts
of the chain
Ø Trans configuration
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Protein synthesis
Gene Func@on
Protein structure
1. Primary structure
2. Secondary structure
3. Tertiary structure
4. Quaternary structure
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Primary structure
u Sequence of amino acids in the polypeptide chain
u Peptide chain has left side N-terminal, right side C-terminal and
remaining amino acids in the chain called residues
Example: Lysozyme has 129 amino acids, all in a very specific order
Hemoglobin—577 amino acids. (E-V) causes sickle cell anemia
ü Sanger Method
ü Edman’s Method
ü Mass spectrometry
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Secondary structure
Describes the shape of the protein
Three type: α-helix and β- pleated sheets, beta bends
Alpha helix
Ø It has spiral structure, consist of
§ Polypeptide back bone
§ Side chains of amino acids extended outward
Ø Formed and Stabilized by
§ Hydrogen bonding between the peptide-bond carbonyl oxygen and
hydrogen atoms of amide group of fourth amino acid in the chain
β- sheets
In β-sheets peptide bond components are involved in hydrogen bonding.
β-sheets can be formed from two or more separate polypeptide chains that are
arranged either parallel or antiparallel
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β-bends
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Tertiary structure
v T h r e e d i m e n s i o n s t r u c t u r e
(conformation) of a polypeptide chain
(globular or fibrous)
Quaternary Structure
Result from combination of two or more polypeptide subunits attached with each
other by non-covalent interactions like H-bonding, ionic or hydrophobic
interaction
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Protein misfolding
Protein misfolding:
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α-helix
β-sheet
Conformational change
Aggregation
Loss of biological
Gain of toxic activity function
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Conformational hypothesis
Protein misfolding is independent of aggregation, which is a non-
necessary end point of conformational changes (the factors inducing
the protein structural changes are e.g. mutations, oxidative stress)
Conformation-oligomerization hypothesis
Slight conformational changes result in the formation of an
unstable intermediate which is stabilized by intermolecular
interactions with other molecules forming small β-sheet
oligomers
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DNA Ubiqui@n
RNA Ribosome
ATP
Chaperones
Proteasome
Accumula5on
(Amyloidoses) Degraded protein
2. Loss of function
Other effect of the misfolded protein may be due to loss of function,
as observed in cystic fibrosis. There is a mutation in the
CFTR(cystic fibrosis transmembrane conductance regulator)
sequence
3. Accumulation
Protein aggregates are sometimes converted to a fibrillar structure.
Fibrils themselves are not toxic but insoluble. Their
accumulation cause tissue damage (amyloidoses)
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Chaperones
Ø assist other proteins to achieve a functionally active
3D structure
Ø prevent the formation of a misfolded or aggregated
structure Hsp 70 - prevents
folding of nascent
Molecular chaperones recognise misfolded protein, bind to chain
the hydrophobic surfaces and inhibit aggregation.
Most of these molecules are heat shock proteins
(formed during thermal damage)-protect against
denaturation.
Alzheimer disease
Ø a progressive degenerative disease of the brain
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Therapy
Ø Considering that protein misfolding and aggregation are central
in the pathogenesis of PCD, a therapy directed to the cause of the
disease should aim to inhibit and reverse the conformational
changes
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