Structure of Proteins

-Beta pleated sheets are the second regular secondary structure in proteins.

- form a zigzag or pleated pattern - peptide backbone of the beta sheet is highly extended -stability from hydrogen bonds between the carbonyl oxygen and amide nitrogen of peptide bonds -these bonds are formed with peptide segments next to each other on the sheet. If the two peptide segments are placed in the same direction ( N-terminal to C-terminal), then they are arranged parallel -peptide segments run in opposite direction the pattern is anti-parallel. Alternate R-groups project above & below the plane of the sheet.

What is Amylidoises?

-Accumulation of Beta sheets in brain and organs -Leads to bone cancer, TB, Arthritis, -Inherited type is Transthyretin

What is Angiotensin?

-Angiotensin II is a peptide with 8 amino acids -hypertensive agent used for stimulating aldosterone release from the adrenal cortex. -Short peptides of biological importance

What is Anserine?

-Anserine is a N-methyl carnosine that exhibits antioxidant effect 5 times as greater - It helps to reduce fatigue -found in the skeletal muscle and brain. -Short peptides of biological importance

What is Aspartame?

-Aspartame is a synthetic dipeptide made of aspartate and methyl ester of penylalanine. -used in artificial sweetener and is 200 times sweeter than sucrose. -Short peptides of biological importance

What is Carnosine?

-Carnosine is a dipeptide of the non protein beta alanyl histidine -found in muscle and brain. -antioxidant effect, used as anti-aging therapy -Short peptides of biological importance

What is Quartenary Structure?

-Combination of two or more polypeptide chains to form a single functional protein -Each polypeptide chain represents a monomer subunit -Two or more monomers together constitute a single functional protein called a oligomeric -Hydrogen bonds, electrostatic bonds, hydrophobic interactions, S-S bonds all stabilize quaternary structure.

What are conjugated proteins?

-Contain non protein prosthetic groups -glycoproteins Prosthetic group is Carbohydrates. -Immunoglobulins, Transferrin, Ceruloplasmin and TSH are glycoproteins -Lipoproteins have a prosthetic group made of lipids and two of them are HDL and LDL -Metalloproteins have a prosthetic group made of metal ions and transferrin, ceruloplasmin and hemoglobin are examples.

What is Gel Electrophoresis?

-Electrophoresis is a separation technique for proteins based on charge properties of molecule -Proteins with net positive charges move towards the cathode that has negative charge and the more positive charges the faster the mobility -Proteins are separated by their molecular mass -So the basis for separation is charge to mass ratio. -Agar gel electrophoresis is one type and uses Polyacrylamide gel electrophoresis (PAGE) -Specific stains or dyes can identify the separated protein bands -The electrophoretic technique used to identify serum protein pattern in health and diseases, identify hemoglobin variants, and know lipoprotein profile in health and disease

What is Enkephalin?

-Enkephalin is a pentapeptide that is formed -found in brain -function of inhibiting the sense of pain -Short peptides of biological importance

What is Glutathione?

-Glutathione is a tripeptide made of glutamate, cysteine and glycine and is called Gamma glutamyl cysteinyl glycine or GSH -component of the cellular antioxidant defense system and a required component for RBC membrane. -Short peptides of biological importance

What are Chaperone proteins?

-Heat Shock Proteins -Synthesis of these proteins is increased at elevated temperatures -they increase the rate of folding by limiting the number of unproductive folding -required for refolding of proteins after they cross cellular membrane -A type of chaperones, called as Chaperonins have an ATPase activity and hydrolyze ATP to facilitate folding -Chaperones also include Cis-trans- prolyl isomerases and Protein disulfide isomerases.

What are two important proteins with large peptide amounts?

-Insulin is a polypeptide hormone which contains 51 amino acids -secreted by beta cells of islets of Langerhans of the pancreas to decrease blood glucose level -it is hypoglycemic. -Glucagon is a polypeptide hormone which contains 29 amino acids -secreted by alpha cells of islets of langerhan of the pancreas to raise the concentration of glucose levels in the blood -it is hyperglycemic.

What is Kallidin?

-Kallidin is a decapeptide and is a powerful vasodilator. -Short peptides of biological importance

Why are Proline and Glycine not favorable for alpha helix?

-Proline disrupts the conformation of the α- helix -produces a bend because the peptide bond nitrogen of proline lacks a hydrogen atom to contribute to a hydrogen bond. -Glycine is not favorable because of its small size -it induces bends in alpha helices -The presence of a large number of charged R groups or large number of bulky R groups are not favorable for the alpha helix

What are some of the different functions of proteins?

-Proteins used for structural support are collagen, Elastin, alpha Keratin, and Dystrophin. -Enzymes are proteins that are used for catalytic purposes. -Proteins are used for transport like Hemoglobin in O2 transport. -Proteins are used as receptors like Rhodopsin and LDL receptor -Proteins Actin, Myosin, Troponin are used for mechanical purposes -Proteins Albumin and Hemoglobin are used for buffering -protein Immunoglobulin is used for defense -Proteins regulate other proteins & Polypeptide hormones -proteins prothrombin and fibrinogen are used for coagulatory purposes -Proteins like Ferritin which is the storage form of iron are used for storage purposes.

What is tertiary structure?

-Tertiary structure is the three-dimensional conformation of a protein or a polypeptide chain -conformation is attributed to assemble secondary structural features such as helices, sheets, bends, turns, and loops which is all determined by the primary structure. -The three dimensional tertiary folding also generates "domains" in proteins. -Disulfide bonds, Hydrogen bonds, hydrophobic interactions, ionic interactions stabilize structure -Disulfide bonds are formed from the sulfhydryl group (-SH) of each of two cysteine residues to form a Cystine residue that is covalently linked. -Hydrophobic interactions occur in two different ways to stabilize the structure. Amino acids with non polar side chains tend to be located in the interior of the polypeptide molecule where they associate with other hydrophobic amino acids compared to amino acids with polar side chains tend to be located on the surface of the molecule. -Hydrogen bonds stabilize the structure as well. Amino acids containing oxygen or nitrogen-bound hydrogen, such as in Serine and Threonine can form hydrogen bonds with oxygen of a carboxyl group or carbonyl group of a peptide bond. -Ionic interactions occur to stabilize the structure when negatively charged groups, such as carboxyl (COO-) in the side chain of aspartate or glutamate can interact with positively charged groups such as amino (-NH3+) in the side chain of lysine.

What is the alpha helix?

-The alpha helix is a polypeptide chain that is coiled around a central axis as a right-handed helix. - The alpha carbon, peptide N and carbonyl C form the back bone of the helix. - Side chains of the amino acids are projected outwards. -The alpha helix structure is stabilized by hydrogen bonds formed between peptide nitrogen of one peptide bond and carbonyl oxygen of 4th peptide bond in linear sequence -Pitch of the helix is 0.54 nm and in each turn there are 3.6 residues -Vertical distance occupied by each amino acid is 0.15 nm. -Proteins that have many alpha helical structures are alpha keratin, Hemoglobin, and myoglobin.

What is protein primary structure?

-The primary structure of a protein is the total number of amino acids used as well as the linear sequence which they are linked by peptide linkage -Primary structure for every protein is unique because a single change in an amino acid changes the chain completely - The primary structure is decided by the gene that codes for the protein -The N terminal residue is found by using the Sangers reagent also called FDNB or Dansyl Chloride -Amino acid sequence for proteins is determined using the reagent phenyl isothiocyanate

What is protein secondary structure?

-The secondary structure of a protein is the folding of short segments also called linear sequences into ordered units -maintained by hydrogen bonding -made of the alpha helix, beta pleated sheets, and loops and bends (turns).

What is Vasopressin and Oxytocin?

-Vasopressin and Oxytocin are a nonapeptide secreted by the posterior pituitary -Vasopressin is an antidiuretic hormone or ADH that regulates water excretion by the kidney -ADH deficiency associated with diabetes insipidus -Oxytcin causes contraction of uterus and is used in induction of labor -Short peptides of biological importance

What are the clinical manifestations of altering primary structure?

-altering primary structure of a protein may result in derangement of its biological activity - In Hemoglobin S (HbS) at the 6th position of beta chain of Hb, Glutamate is replaced by Valine -The clinical manifestation is now Sickle cell anemia - In Hemoglobin M (HbM) a vital Histidine residue is replaced by Tyrosine and the clinical manifestation is Methemoglobinemia a blood disorder - In the case of Cystic Fibrosis Transmembrane Regulatory (CFTR) gene mutation results in lack of a single Phenylalanine in CFTR protein -Normal CFTR protein contains 1480 amino acids -impairs the chloride and fluid secretary capacity of CFTR protein resulting in impairment of pancreatic, intestinal and lung functions.

What is the structure of proteins?

-link together by peptide bonds also called peptide linkages forming peptides or proteins. -peptide bond is formed when the amino group of an amino acid reacts with the carboxyl group of another amino acid forming a covalent amide linkage -Peptide bonds are rigid, planar, have double bond character, are in trans form, and have no freedom to rotate around the peptide bond between the carbonyl carbon and nitrogen of peptide bond. -Amino acid ends are called free amino terminal

What is denaturation?

-loss of native structure (conformation) of proteins is called denaturation -change of physicochemical properties, viscosity is increased, proteins become least soluble and denaturation of biological activity occurs -primary structure of protein remains unaltered -Mostly irreversible but reversible in certain cases -Causes for denaturation are physical by heat, vigorous mixing, x-rays, uv-radiation, chemically by acids, alkali, organic solvents, salts of heavy metals -Digestibility of proteins is increased in the stomach by HCl of gastric juice which makes dietary proteins digestible

What is Prion disease?

-proteinaceous infectious agent and it causes Prion diseases which is Transmissible spongiform encephalopathies -Prion diseases are fatal neurodegenerative diseases, characterized by spongiform changes and neuronal loss that results from the deposition of insoluble protein aggregates in neural cells. -Prion diseases can be acquired either through infection like mad cow disease or inherited mutation like Creutzfeldt Jacob Disease (CJD). -normally found in the brain and is represented as PrPc -The disease causing prion protein is represented as PrPsc -PrPsc has the same amino acid composition as that of normal prion protein PrPc but the PrPsc is folded into different conformation -PrPc has many alpha helix and little or no β-sheet while the PrPsc possesses many β-sheet structures -The beta sheet structures favor aggregation of PrPsc to form complexes, that are resistant to proteolytic cleavage which means once formed, PrPsc acts as a template & triggers transformation of other native PrPc proteins, so that the transformed proteins also acquire the misfolded beta sheet structures.

Loops and Bends

-secondary structures exists as alpha helices and beta sheets, loops, turns or bends. -Turns or bends refer to short sequences of amino acids that join the two units of secondary structure like two adjacent strands of beta pleated sheets -A turn involves four amino acid residues -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 is Super Secondary Structure?

The super secondary structure are -structural motifs in the proteins which form the core region of the molecule -produced by close packing of the side chains of adjacent secondary structural components -connected by loop regions like beta bends -common type of super secondary structure is alpha to alpha which is Helix-loop-helix found in proteins that function as transcription factors -Another is beta-alpha-beta, beta-meander is 2 or more consecutive antiparallel beta strands -beta-Barrel which consists of many parallel strands arranged in a barrel shape