General structure of Proteins Flashcards
What are proteins and peptides made of and how arethey linked?
- Proteins and peptides are made up of amino acids
- In proteins/peptides the individual amino acids are linked to each other by peptide bonds (linkages)
Formation of Peptide bonds:
•A peptide bond is formed when an amino group of one amino acid reacts with a carboxyl group of another amino acid.
What is a dipeptide and a tripeptide?
Dipeptide
Two amino acids linked by a peptide linkage form a dipeptide
Example:
Ala-gly Gly-cys
Tripeptide
Three amino acids linked by 2 peptide bonds form a tripeptide
glu-cys-gly Ala-val-phe
Explain the shape of the peptide bond, the bonding character, any rotation around the peptide bond and what form does it exist in?
- Peptide bond is rigid and planar.
- It has partial double bond character.
- No freedom of rotation around the peptide bond
- Exists in trans form
Describe these and explain what they function as?
Carnosine, Anserine, Glutathione, Enkephalin, Angiotensin 11
**Carnosine: **
A dipeptide (β-alanyl histidine)
Present mainly in muscle & brain
Has antioxidant effect
Recommended as anti- aging therapy
** Anserine:**
It is N-methyl carnosine
Also exhibits antioxidant effect
** Glutathione:**
It is a tripeptide consisting of glutamate, cysteine & glycine (Gamma glutamyl cysteinyl glycine).
It is conventionally written as GSH
It is an important component of cellular antioxidant defense system.
It is an essential component, required for integrity of RBC membrane
**Enkephalin:** Pentapeptide (made up of 5 amino acids) found in brain.
It inhibits sense of pain
** Angiotensin II:**
A peptide with 8 amino acids
It is a hypertensive agent
It stimulates release of aldosterone from adrenal cortex
** Vasopressin ( antidiuretic hormone or ADH):**
Contains 9 amino acids. Secreted by posterior pituitary gland. It regulates water excretion by kidney. ADH deficiency is associated with diabetes insipidus
** Oxytocin:**
It is also made up of 9 amino acids. Secreted by posterior pituitary gland.
Causes contraction of uterus.
Used in induction of labor
Aspartame:
A synthetic dipeptide made up of aspartate &
methyl ester of phenylalanine
Artificial sweetener (200 times sweeter than
sucrose)
What are the Polypeptides of Biological Significance (2)?
Insulin – Polypeptide hormone Containing 51
amino acids.
Glucagon - Polypeptide hormone with 29 amino
acids
Both are involved in the regulation of fuel
metabolism
What is the general importance of proteins(8) ?
- Proteins are polymers of amino acids.
- Are synthesized in living cells in response to genetic information
- Exhibit diverse functions in living system
- Structural: Collagen, Elastin, α-Keratin, Dystrophin etc
- Catalytic: Most of the enzymes
- Transport: Hemoglobin (O2 transport),
- Receptor: Rhodopsin, LDL receptor
- Mechanical: Actin, Myosin, Troponin etc
- Buffering: Albumin, Hemoglobin
- Defense: Immunoglobulins
- Regulatory: Protein & Polypeptide hormones
Several proteins contain non-prosthetis groups such proteins are called what? Give examples(3)
•Several proteins contain non protein prosthetic groups. Such proteins are called as conjugated proteins
- Examples:
- Glycoproteins (Prosthetic group-carbohydrates)
- (A large no. of proteins are glycoproteins)
- Lipoproteins (Prosthetic group – Lipids)
- (Examples – HDL, LDL, etc)
- Metalloproteins (Prosthetic group – metal)
- (Examples: Transferrin, ceruloplasmin, hemoglobin etc)Structure of proteins can be explained at 4 levels.Primary, secondary, tertiary and quaternary structures
What does the primary structure of a protein refer to?
•Primary structure of a protein refers to;
— a) Total No. of amino acids,
— b) Nature/types of amino acids
— c) The linear sequence of amino acids.
- Amino acids are linked by peptide linkage.
- Primary structure is unique to each of the proteins.
- Primary structure is decided by the gene that codes for the protein
Explain how the protein/polypeptide is structured in terms of the N-terminus and C-terminus
- Primary structure is decided by the gene that codes for the protein
- In a protein/ polypeptide chain there is a free α – amino group at one end, which is N-terminal end (amino terminal end). Whereas at the other end, called as C- terminal end/carboxy terminal end there is a free α- carboxyl group
- Numbering of amino acids of a protein starts from N- terminal end and ends at C –terminal end.
•That means N- terminal amino acid is the first residue and C-terminal amino acid is the is the last residue.
- what can the n-terminal amino acid residue be identifed by?
- What is the amino acids sequence of a protein determined by?
- What is Frederick Sanger?
- How many amino acids does growth hormone, myoglobin, CFTR protein, a-chain of hemoglobin and b-chain of hemoglobin have?
- N- terminal amino acid residue can be identified by using Sanger’s reagent (FDNB) or Dansyl Chloride
- Amino acid sequence of a protein is determined by Edman’s degradation method using the reagent Phenyl isothiocyanate
- Frederick Sanger determined the primary structure of insulin in 1955, – received Nobel prize (1958) for this work.
- Growth hormone – 191 amino acids
- Myoglobin - 153 amino acids
- CFTR protein – 1480 amino acids
- α - chain of hemoglobin – 141 amino acids
- β - chain of hemoglobin – 146 amino acids
Alteration in primary structure of a protein may result in derangement of its biological activity. What are the examples (3)?
- Hemoglobin S (Hb S)– Here at 6th position of β- chain of Hb, glutamate is replaced by valine.
- –Clinical manifestation – Sickle cell anemia
- Hemoglobin M -where a vital Histidine residue is replaced by tyrosine – leads to methemoglobinemia
- Cystic Fibrosis Transmembrane Regulatory (CFTR) protein in Cystic Fibrosis - In majority of cases of cystic fibrosis (an autosomal recessive disorder, commonly seen among Caucasians) a gene mutation results in lack of a single phenylalanine in CFTR protein (Normal CFTR protein contains 1480 amino acids). This alteration drastically impairs the chloride and fluid secretary capacity of CFTR protein, thereby resulting in impairment of pancreatic, intestinal and lung functions
What is the secondary structure of protein ? What is it maintained by? Whar are the two major types of secondary structures?
Secondary Structure:•It refers to folding of short segments of protein
into geometrically ordered units.
•Here linear sequences of amino acids of a protein chain participate in secondary structure.
•Maintained by hydrogen bonding
•Two major types of secondary structures are;
•α – helix and β – pleated sheets
•In addition loops and bends (turns) are also form a part of secondary structures
Who discovered the alpha helix? What is alpha helix stabilized by? How many residues are there in each turn, vertical distance occupied by each amino acid. What disrupts the conformation of the a-helix producing bends? What are some examples of protein rich in a-helical structure?
- Discovered by Pauling and Corey in 1952
- Polypeptide chain is coiled around a central axis as right handed helix
- α-carbon, peptide N and carbonyl C form the back bone of the helix
- The side chains of amino acids are projected radially outwards
- α - Helix structure is stabilized by H-bonds. The hydrogen bond is formed between peptide (amide) nitrogen (N) of one peptide bond and carbonyl oxygen (C=O) of 4th peptide bond in linear sequence
- Pitch of the helix is 0.54 nm. In each turn there are 3.6 residues, Vertical distance occupied by each amino acids is 0.15 nm
- Proline disrupts the conformation of the α- helix, producing a bend (Because the peptide bond nitrogen of proline lacks a hydrogen atom to contribute to a hydrogen bond )
- Glycine , because of its small size, also often induces bends in α –helices
- Presence of large number of charged R groups or large number of bulky R groups are not favorable for α –helix
- Examples of proteins rich in α-helical structure:
- α – keratin, Hemoglobin, myoglobin
What are b-pleated sheets? What makes b-pleated sheets different from a-helix?
Where are the hydrogen bonds formed ? If two segments are placed in the same direction , what is it called? if two segments are placed in different direction, what is it called?
- The second (hence “beta”) recognizable regular secondary structure in proteins is the β- pleated sheet.
- The amino acid residues of a β- sheet, when viewed , form a zigzag or pleated pattern
- Unlike the compact backbone of the α - helix, the peptide backbone of the β sheet is highly extended.
- But like the α - helix, β sheets also derive much of their stability from hydrogen bonds between the carbonyl oxygen and amide nitrogen of peptide bonds.
- However, in contrast to the α - helix, **these bonds are formed with adjacent peptide segments of the sheet **
•Hydrogen bonds are formed between carbonyl oxygen and peptide nitrogen.
•If the two peptide segments are placed in the same direction ( N-terminal to C-terminal), then they are said to be arranged parallel
•
•If the peptide segments run in opposite direction the pattern is anti-parallel
•
•Alternate R-groups project above & below the plane of the sheet.
What are loops and bends? What is a turn? What amino acids are present in turns?
•Turns or bends refer to short sequences of amino acids that join the two units of secondary structure, such as two adjacent strands of β - pleated sheets.
•A turn involves four amino acid residues, in which the first residue is hydrogen-bonded to the fourth, resulting in a tight 180-degree turn.
Proline and glycine often are present in these turns
What are super secondary structure? What are the common types of super secondary structures?
•They are Structural motifs in the proteins
•Form core region of the molecule
•Usually produced by close packing of the side chains of adjacent secondary structural components
•Connected by loop regions like β-bends.
•Some of the common types of super secondary structure are:
–α-α (Helix-loop-helix)- found in proteins that function as transcription factors
–β-α-β
–β-meander- 2 or more consecutive antiparallel β-strands
–β-Barrel - consists of many parallel strands arranged in a barrel shape
