Proteins Flashcards

Question

How can 2 a.a be joined

Answer 1

covalently in a condensation reaction These are amide linkages between the α-carboxyl group of one a.a and the α-amino group of the other. • Side chain determines the property of protein

Answer 2

Peptide bonds are not broken in normal denaturing conditions. – has a partial double bond character: (Shorter than a single bond ) –Is rigid (between C1 and N is always closer to 180 ) and planar (due to the delocalization of the electrons from the double bond) –Exist in trans configuration –Is uncharged but polar prevents free rotation around the bond :between the carbonyl carbon and the nitrogen of the peptide bond. • Peptide bond is uncharged- neither accepts nor release protons. Generally peptide bond is not available for chemical reaction except for hydrogen bond formation. Polarity depends on the N-terminal amino group, C- terminal carboxy group and any ionized chains present in the side chain.

Answer 3

• Free N terminal is written to the left • Free Carboxyl terminal to the right • A.a are read from the N to C terminal • A.a residue having the suffix “ine, an, ic, ate” are changed to “yl” except the c-terminal

Answer 4

peptide bonds are cleaved and a.a are released , a.a is separated by cation-exchange chromatography.

Answer 5

Positive tesr is purple coloured complex

Answer 6

• Edman Degradation

Answer 7

• If the nucleotide sequence is determined, from the genetic code it is possible, to translate the sequence of nucleotides into the corresponding a.a of that polypeptide.

Answer 8

• Mainly four organizational level • Primary, Secondary, Tertiary, Quaternary. • The complexity increases • Ranges from simple proteins to multifunctional proteins

Answer 9

• Sequence of a.a in a protein (joined by peptide bonds) • Includes the location of disulfide bond • Deviation and abnormality in the a.a sequence may result in improper folding and loss of normal function

Answer 10

• The conformation of the polypeptide backbones of proteins • Commonly they form a regular arrangements with a.a close to each other : arrangements are due to the partial double bond character of the peptide bond • 2ndry structure includes α-helix, β-sheet and β-bend • Hydrogen bonds and Vander Waals force stabilize the 2ndry structure mainly the α-helix

Answer 11

• A common motif in the IIry structure of proteins • The α-helix is a right- or left-handed coiled conformation • Resembles a spring, in which every backbone N-H group donates a H bond to the backbone C=O group of the a.a four residues earlier ( hydrogen bonding). • Spiral structure • Tightly packed, coiled polypeptide backbone core. Side chain extend outwards Stabilized by H bonding b/w carbonyl oxygen and amide hydrogen. Amino acids per turn - 3.6 Pitch is 5.4 A Alpha helical segments are found in many globular proteins like myoglobins, troponin- C etc. • It has the lowest energy and is the most stable form (stability increases with hydrogen bond formation) • Some a.a disturb the helix • proline may insert a kink, • charged a.a form ionic bond and disturb the arrangement • bulk side chain a.a may also interfere

Answer 12

Unlike the alpha helix β-chain are composed of two or more peptide chains (strands) or segments of peptide chain • All the peptide bond component are involved in hydrogen bonding • The hydrogen bond is perpendicular • Hydrogen bonds may be inter or intra chain bonds • They may be parallel (C–terminals on the same side or antiparallel (C-terminals on the opposite side) or mixed (both )

Answer 13

Predominant protein type in globular proteins • Compact structure • Predominantly found in cytosol & surface of protein molecule • Connect strands of anti-parallel β-sheets • Contain mainly proline (kink), glycine (smallest a.a)

Answer 14

• Some polypeptides may have a loop or coil and have less regular structure (“random coil”) Secondary structure

Answer 15

• Combines all IIry structure & assembles together • Side chains of adjacent IIry structure elements assemble close to each other & folds into a protein

Answer 16

• IIIry structure is considered to be largely determined by the protein's Iry or the sequence of a.a of which it is composed of • In globular proteins , IIIry interactions are frequently stabilized by the sequestration of hydrophobic a.a residues in the protein core, from which water is excluded, & by the consequent enrichment of charged or hydrophilic residues on the protein's water-exposed surface.

Answer 17

four types of bonding interactions between "side chains" including: hydrogen bonding, salt bridges, disulfide bonds, and non- polar hydrophobic interactions.

Answer 18

• Disulfide bonds are formed by oxidation of the sulfhydryl groups on cysteine. • Two disulphide-linked cysteines are referred to as cystine • Protein chains or loops within a single chain are held together by the strong covalent disulphide bonds. e.g. albumin

Answer 19

• Hydrogen bonding between "side chains" occurs in a variety of circumstances. • The most usual cases are between two alcohols, an alcohol and an acid, two acids, or an alcohol and an amine or amide.

Answer 20

Salt bridges • Result from the neutralization of an acid and amine on side chains. • The final interaction is ionic between the positive ammonium group and the negative acid group.

Answer 21

hydrophobic interactions of non-polar side chains are believed to contribute significantly to the stabilization of the IIIry structures • Non-polar groups mutually repel water & other polar groups & results in a net attraction of the non-polar groups for each other. e.g. Ala, Val, Leu, and Ile interact in this way. • Benzene (aromatic) rings on Phe &Tyr can "stack" together.

Answer 22

• Arrangement of protein with two or more polypeptide chain (subunits) – 2subunit-dimeric – 3subunit-trimeric • These sub units are held together by non-covalent interactions (H- bond, ionic bonds, hydrophobic interaction)

Answer 23

Simple — globular and scleroproteins ( fibrous proteins ) Conjugated Derived — primary & secondary

Answer 24

Albumins Globulins Prolamins Glutelins Histones Protamins Globins

Answer 25

Collagen Elastins Keratins

Answer 26

Nucleoproteins Chromoproteins Glycoprotein Phosphoprotein Lipoprotein Metalloprotein

Answer 27

Proteans Metaproteins Coagulated proteins

Answer 28

Proteoses Peptones Polypeptides Simple peptides Amino acids

Answer 29

Shape. Axial ratio greater > 10 Axial ratio less than 10 _ . Long & narrow Round/spherical Solubility. Insol. Sol Purpose. Structural. Functional Example Collagen, myosin, Enzymes, Hb, insulin, fibrin, Actin,a-Keratin, Immunoglobulin elastin Durability Less sensitive to changes More sensitive In pH, temp etc

Answer 30

• Most abundant protein in human • Rigid insoluble protein • In some tissue it is dispersed in the form of gel e.g. extracellular matrix / the vitreous humour • In some other tissues found as tight parallel fibres: e.g. tendon • Collagen may be stacked : e.g. cornea

Answer 31

• Formed in fibroblast or in the osteoblast of bones & chondrocytes • Secreted into the extracellular matrix after enzymatic modification • Monomers aggregates & cross links to form collagen fibrils

Answer 32

• Genes to transcription to Translation to protein • Formation of Pro α-chains • Hydroxylation • Glycosylation • Assembly & secretion of procollagen • Extracellular cleavage of procollagen • Formation of collagen fibrils • Cross link formation

Answer 33

• In the RER selective hydroxylation of proline & lysine takes place at the Y location from glycine Gly-X-Y • Hydroxylation enzymes (prolylhydroxylase & lysyl hydroxylase) requires molecular oxygen and vitamin C • Hydroxyl lysine & hydroxyl proline enhances the cross linking & strengthen the collagen

Answer 34

•Hydroxyl lysine can be further modified with glucose or glucosyl – galactose

Answer 35

Lysyl oxidase oxidatively deaminates some lysyl & hydroxylysyl residues giving rise to aldehyde groups (allysine, hydroxyallysine) 3 pro-α-chains assemble - is initiated by the disulfide cross linking of the C-terminus helical structure in the middle & non-helical structure at the C & N terminal Collagen molecule to microfibrils ( quarter staggered arrangement ) to fibrils • This cross links with neighbour lysyl, & hydroxyl residues & forms covalent cross links providing tensile strength Note: 1. Any interference to the cross linking affects the stability of the collagen 2. Deficiency of the above processes may lead to scurvy

Answer 36

• The tropocollagen or "collagen molecule" is a subunit of larger collagen aggregates such as fibrils. • Approximately 300 nm long and 1.5 nm in diameter, made up of three polypeptide strands (called alpha chains), each possessing the conformation of a left- handed helix These three left-handed helices are twisted together into a right- handed coil, a triple helix or "super helix", the quaternary structure are stabilized by numerous H-bonds.

Answer 37

Amino acids approx. 1 nm Tropocollagen approx. 300 nm Fibrils approx. 1 um Fibres approx. 10 um

Answer 38

Fibril forming • Type I : This is the most common collagen type found in skin, bone, tendon, blood vessel, cornea Type II Cartilage, intervertebral disk, vitreous body Type III Blood vessels, fetal Network forming Type IV Basement membrane Type VII beneath stratified squamous epithelia Fibril-associated Type IX cartilage Type XII tendon, ligaments, some other tissues

Answer 39

Ehlers-Danlos Syndrome ( circus man syndrome ) Osteogenesis imperfecta (brittle bone disease)

Answer 40

Contrast to collagen elastin is stretchable and rubber like • Insoluble protein synthesized from a precursor, tropoelastin (soluble polypeptide) • Composed of small nonpolar a.a such as glycine, alanine & valine • Even though it is rich in proline and lysine contains only little hydroxylated a.a

Answer 41

–Found in lungs, elastic ligaments, wall of large arteries

Answer 42

• Elastin fibres are formed as a 3D network of cross linked polypeptides with an irregular conformation • Four lysine side chains from 4 different elastin molecules covalently join to produce desmosine cross links Extensively interconnected rubbery network-to- stretch and bend

Answer 43

• This enzyme inhibits number of proteolytic enzymes that hydrolyse & destroy protein- produced in liver • Inhibits mainly trypsin • It also inhibits neutrophil elastase which degrades elastin in the alveoli

Answer 44

• one single purine base mutation (GAG to AAG - lys for glu) • mutation causes the normally monomeric α -AT to misfold, polymerize, and aggregate within the RER of hepatocytes • This causes a decrease in the secretion of α -AT by the liver. • Consequently, blood levels of AAT are reduced, decreasing the amount that gets to the lung.

Answer 45

• The polymer that accumulates in the liver may result in cirrhosis • Lung tissue cannot regenerate • Though lung is exposed to low level of neutrophil elastase its activity is inhibited by α-1 antitrypsin • In deficiency of α-1 Antitrypsin Emphysema may result smokers with α-AT deficiency are at more risk than non smokers to develop emphysema Tx: Administration of α-1 AT and inhibitors of neutrophil elastase

Answer 46

•They are tough fibres found in hair, nails & outer epidermal layer of mammals •Each poly peptide has an α-helical structure •They are rich in cysteine and form disulphide bonds Has weak and strong links

Answer 47

• Denaturation is the process where protein loses its native secondary, tertiary and /or quaternary structure Note: Iry structure is not necessarily broken in denaturation

Answer 48

pH Temp Ionic strength Solubility

Answer 49

inherited blood disorder associated with Hb

Answer 50

abnormal form of hemoglobin that may cause mild anaemia

Answer 51

• have spheroidal shape • have variable molecular weights, • In water highly soluble

Answer 52

catalysts, transporters & regulators of metabolic pathways & gene expression.

Answer 53

• Is an example of a prosthetic group, (a non-protein group tightly associated with the protein). • It sits in a hydrophobic pocket of haemoglobin having 2 histidine one on either side of the haem. • Consists of Fe2+ in a ring, known as a porphyrin. • Fe2+ which is the site of oxygen binding, coordinates with the four nitrogen in the center of the ring, which all lie in one plane. • iron is also bound strongly to the globular protein via the imidazole ring of the histidine residue below the porphyrin ring. • A sixth position can reversibly bind oxygen by a covalent bond, completing the six ligands. • When oxygen is not bound, a very weakly bonded water molecule fills the site.

Answer 54

• The iron in the Fe3+ state (Methaemoglobin) cannot bind oxygen. • Binding, oxygen temporarily oxidizes Fe2+ to Fe3+. • The enzyme Methaemoglobin reductase reactivates to Fe2+

Answer 55

• Present in heart and skeletal muscle. • Single chain globular protein of 153 amino acids • It gives muscle tissue a distinct red or dark gray colour.

Answer 56

• Functions both as a reservoir for oxygen, and as an oxygen carrier that increases the rate of transport of oxygen within the muscle cell.

Answer 57

• Mb is similar to Hb in structure and sequence but it is a monomer (Compare the tetramer structure of Hb) hence lacks cooperative binding. • Globin (α-helical protein) consists of a single polypeptide chain (structurally similar to the individual subunit polypeptide chains of Hb) • Polypeptide chain is folded into eight stretches of α-helix which is disturbed by proline. • Interior of the myoglobin molecule is composed almost entirely of nonpolar a.a (binds the haem group by non covalent bond) except two histidine residues. • one, binds directly to the iron of haem and the other helps stabilize the binding of O2to Fe2+ • charged amino acids are located almost exclusively on the surface of the molecule,

Answer 58

• Myoglobin is an unusual protein as it comprises exclusively (80%) of α-helices joined by short loops. • Most proteins have both α-helices and β-sheets.

Answer 59

-Higher O2 affinity. - cooperative binding = sigmoidal curve -Responds to muscle's. - responds to O2 availability O2 needs - curve that flattens - O2 binding properties of Hb regulated - 1 Haem group so 1 O2. By interaction with allosteric effectors - can transport H+ and CO2

Answer 60

• Is an iron containing oxygen transport metalloprotein in the RBC. .

Answer 61

• Function is to transport 1.oxygen from the lungs to the capillaries of the tissues. 2.CO2 from the capillaries of the tissues to lungs. 3.NO: e.g S-nitrosohemoglobin (SNO-Hb), which can deliver the NO to areas of hypoxia or restricted blood flow I4.mportant role as an efficient buffer (pH of histidine side chain)

Answer 62

• Haemoglobin A, the major hemoglobin in adults, is composed of four polypeptide chains—2 α chains and 2 β chains—held together by noncovalent interactions • Each subunit has stretches of α-helical structure, and a haem-binding pocket similar to that of Mb.

Answer 63

• The haemoglobin tetramer can be envisioned as being composed of two identical dimers, (α1β1)and (α2β2) in which the numbers refer to dimers one and two. • The two polypeptide chains within each dimer are held tightly together, primarily by hydrophobic interactions In this instance, hydrophobic amino acid residues are localized not only in the interior of the molecule, but also in a region on the surface of each subunit. • Inter chain hydrophobic interactions form strong associations between α-subunits and β-subunits • Ionic and hydrogen bonds are also present • The two dimers are able to move with respect to each other, being held together primarily by polar bonds. • The weaker interactions between these mobile dimers result in the two dimers occupying different relative positions in deoxyhaemoglobin as compared with oxyhaemoglobin

Answer 64

• Salt bridges (ionic bond) • Hydrogen bond • Hdrophobic interactions

Answer 65

Taut (T-tensed) Relaxed (R) form

Answer 66

Deoxy form of haemoglobin • The two αβ dimers interact through a network of ionic bonds and hydrogen bonds that constrain the movement of the polypeptide chains. Some of these bonds broken in oxygenated state

Answer 67

• Binding of oxygen to Hb causes the rupture of some of the ionic bonds and hydrogen bonds between the αβ dimers. • Here the polypeptide chains have more freedom of movement

Answer 68

• Is synthesized in a complex series of steps. • The haem part is synthesized in the mitochondria and cytosol of immature red blood cells • The globin protein parts are synthesized by ribosomes in the cytosol

Answer 69

Most of CO2 produced in metabolism is hydrated and transported as bicarbonate ion • Some CO2 is carried as carbamate bound to the uncharged α-amino groups of hemoglobin • CO2 is more readily dissolved in deoxygenated blood, • Binding of CO2 stabilizes the R resulting in a decrease in its affinity for oxygen. • In the lungs, CO2 dissociates from the haemoglobin, and is released in the breath.

Answer 70

• Oxyhaemoglobin is formed during respiration when oxygen binds to the haem component of the protein Hb in RBC. • Deoxyhaemoglobin is the form of haemoglobin without the bound oxygen.

Answer 71

• CO binds tightly to haemoglobin • Bind to one/four of the haem sites • Oxygen dissociation curve becomes hyperbolic (left shift) • Unable to release oxygen to the tissues • Affinity of haemoglobin for CO is 200-300 times greater than that of oxygen

Answer 72

• Determining the presence and severity of anaemia • Screening polyycythaemia • Estimation of red cell indices • Selection of blood donors • Response to specific therapy in anaemia