1 / 31

STRUCTURAL ORGANISATION

BIOCHEMISTRY

mprasadnaidu
Download Presentation

STRUCTURAL ORGANISATION

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. PROTEIN STRUCTURAL ORGANIZATION M.Prasad Naidu MSc Medical Biochemistry, Ph.D.Research Scholar

  2. Our life is maintained by molecular network systems Molecular network system in a cell (From ExPASy Biochemical Pathways; http://www.expasy.org/cgi-bin/show_thumbnails.pl?2)

  3. Proteins play key roles in a living system • Three examples of protein functions • Catalysis:Almost all chemical reactions in a living cell are catalyzed by protein enzymes. • Transport:Some proteins transports various substances, such as oxygen, ions, and so on. • Information transfer:For example, hormones. Alcohol dehydrogenase oxidizes alcohols to aldehydes or ketones Haemoglobin carries oxygen Insulin controls the amount of sugar in the blood

  4. Biology/Chemistry of Protein Structure Assembly Folding Packing Interaction Primary Secondary Tertiary Quaternary S T R U C T U R E P R O C E S S

  5. Primary structure • 1.Primary structure denotes the number and sequence of aminoacids in the peptide chain and location of disulfide bonds,if present • 2.The higher levels of organisation are decided by the primary structure. • 3.The primary structure is maintained by the covalent peptide bond. • 4.peptide bonds are not broken down by conditions that denature proteins,such as heating or high concentrations of urea.

  6. 5.Peptide bonds need prolonged exposure to a strong acid or base at elevated temperatures to hydralyse non enzymatically.

  7. CHARECTERSTICS OF PEPTIDE BOND • 1.Partial double bond.It is rigid and planar.so there is no freedom of rotation. • 2.The C-N bond is trans in nature because of steric interference of the R-groups when in the cis position. • 3.the distance is 1.32A*which is midway between single bond(1.49A*) and double bond (1.27 A*) • 4.The side chains are free to rotate on either side of peptide bond.

  8. 5.The angles of rotation known as “Ramchandran angles”,determines the spatial orientation of peptide chain.

  9. NUMBERING OF AMINOACIDS PSEUDOPEPTIDE; Eg: Glutathione (gamma glutamyl-cysteinyl-glycine) FORMATION OF PEPTIDE BOND; • Nameing of aminoacids in a polypeptidechain; • By changing the suffix” in” to “yl” Eg; NH2-Gly-Ala-Val-COOH glycyl-alanyl-valine

  10. BRANCHED AND CIRCULAR PROTEINS • Generally ,primary structure is linear. • Branched proteins are produced by interchain disulfide bond • Eg:insulin • Circular protein: Eg; Gramicidin.

  11. Clinical significance: • A single aminoacid change (mutation) in the linear sequence may have profound biological effects on the function. • Eg: • Sickle cell anemia: • HbS is produced by substitution of Valine in place of Glutamic acid in the 6th position of beta chain of HbA.

  12. Secondary structure • Secondary structure denotes the configurational relationship between residues which are about 3-4 aminoacids apart in the linear sequence. • It is maintained by Hydrogen bonds, Electrostatic bonds, Hydrophobic bonds, Van der waals forces.

  13. 1.Alpha helix • 1.Alpha helix is a spiral structure.Polypeptide bonds form the back-bone core and the side chains of aminoacids extend outward to avoid interfering sterically with each other. • 2.It is the most common and stable conformation for a polypeptide chain. abundent in hemoglobin and myoglobin ---- globular and flexible molecule. absent in chymotrypsin.

  14. 3.Present in keratins,fibrous proteins ------ major component of hair and skin--- rigidity is determined by number of disulfide bonds in it.

  15. 4.The structure is stabilized by hydrogen bonds between NH and C=O groups of the main chain. • 5.Each turn is formed by3.6 residues.the distance between each aminoacid residue is 1.5 A*. • 6.It is generally right handed because aminoacids found in proteins are of L-variety,which exclude left handedness.

  16. Aminoacids that disrupts an alpha-helix; 1.Proline and Hydroxyproline will not allow the formation of alpha-helix because • a) its secondary aminogroup is not geometrically copatible with the right handed spiral of alpha-helix. • b)it inserts a kink in the chain,whichinterfers with the smooth,helical structure. 2.Large number of charged aminoacids also disrupt by forming ionic bonds or by electrostatically repelling each other.

  17. 3.aminoacids with bulky side chains ,such as tryptophan,valine,isoleucine,that branch at beta carbon,if present in large numbers---- also interferes.

  18. 2.Beta pleated sheet: • 1.the surfaces of beta-sheets appear pleated” ----beta pleated sheets. • 2.it is formed by the polypeptide chain folding back on itself. • 3.The polypeptide chains are fully extended.The distance between adjacent aminoacids is 3.5 A*. • 4.It is stabilized by hydrogen bonds between NH and C=O groups of neighboring polypeptide segments. • 5.Strands run in same direction regard to the amino and carboxy terminal ends of poly peptide chain--------------- parallel. • Eg; Flavodoxin

  19. 6.Strands run in opposite direction --------------- antiparallel • Eg; Silk fibroin • 7.Both are present in Carbonic anhydrase. • 3.Beta bends(reverse turns,Beta-turns): • 1. are formed by the abrupt U-turn folding of chain.Intrachain disulfide bridges stabilize these bends. • 2.it reverse the direction of a polypeptide chain to form a copact,globular shape. • 3.they are usually present on the surface of protein molecules. • 4. it usually composed of 4 aminoacids,among one is • Proline -----causes kink” • Glycine ----smallest

  20. 4.Non repetitive secondary structure: • 1.small part of polypeptide chain forms loop or coil. • 2. it is less regular structure than alpha helix and beta pleated sheets. • 5.SUPER SECONDARY STRUCTURE(MOTIFS): • Produced by packing side chains from adjascent secondary structural elements close to each other.

  21. Eg; Zinc finger motif– common .found in transcription factors. • COLLAGEN; • It is a triple helix. • Formed by mainly • Proline – kinks because of its ring structure • Glycine- fits in to the restricted spaces where the three chains of the helix come together.

  22. 3.TERTIARY STRUCTURE • 1.Tertiary structure denotes three dimensional structure of whole protein. • 2.It defines steric relationship of aminoacids which are far apart from each other in linear sequence,but are close in three-dimensional aspect. • 3.It is thermodynamically most stable. • 4.it refers to folding of domains and to the final arrangement of domains in the polypeptide.

  23. 4. It is maintained by Hydrogen bonds, Electrostatic bonds, Hydrophobic bonds, Van der waals forces. 1.DOMAINS; 1.These are fundamental functional and three dimensional structural units of polypeptides. 2.The core of domain is built from combinations of super secondary structural elements (motifs). • 5.Domain is a compact globular unit of protein.These are connected with relatively flexible areas of protein. • Eg; Phenyl alanine hydroxylase enzyme contains 3 domains,oneregulatory,one catalytic and one protein-protein interaction domains.

  24. 2.Protein folding: • 1.Interactions between the side chains of aminoacids determine how a long polypeptide chain folds into intricate three-dimensional shape of the functionalprotein. • 2.interactions involving hydrogen bonds,hydrophobic bonds and disulfide bonds all exert an influence on the folding process. • 3.ROLE OF CHAPERONS IN PROTEIN FOLDING;

  25. 1.CHAPERONES” are required for proper folding of many species of proteins. • 2.chaperones-also known as heat shock”proteins- interact with the polypeptide at various stages during the folding process.

  26. 4.QUATERNARY STRUCTURE • 1.It denotes polypeptide subunits aggregate to form one functional unit. . • 2.It is maintained by Hydrogen bonds, Electrostatic bonds, Hydrophobic bonds, Van der waals forces.

  27. 3.Depending on the number of polypeptide chains,protein is termed as 1.monomer, 2.dimer, Eg;creatine kinase 3.tetramer. Eg;1.Hemoglobin, 2. Immunoglobulin.

  28. PROTEIN MISFOLDING • 1.protein folding is trail and error process that can sometimes result in improperly folded molecules. • 2.misfolded proteins are usually tagged and degraded with in the cell. • 3.if they accumulate causes diseases. • Eg; • 1.Amyloidoses:

  29. Seen in Alzeimers disease; • It is a neuro degenerative disease charecterised mainly by cognitive impairment.

  30. B.PRION DISEASE; • 1.PRION PROTEIN IS A CAUSATIVE of transmissible spongiform encephalopathies, • Creutzfeldt-jakob disease in humans, • Scrapie in sheep, • Bovine spongiform encephalopathy in cattle.

  31. Summary • Proteins are key players in our living systems. • Proteins are polymers consisting of 20 kinds of amino acids. • Each protein folds into a unique three-dimensional structure defined by its amino acid sequence. • Protein structure has a hierarchical nature. • Protein structure is closely related to its function. • Protein structure prediction is a grand challenge of computational biology.

More Related