Proteins Flashcards
(83 cards)
1
Q
Peptide bond?
A
- covalent amide bond between carboxyl group of one amino acid and amino group of another
- not ionizable
- forms H bonds
- water soluble
2
Q
N terminal end has free what? C terminal end?
A
N- free amine group
C- free carboxyl group
3
Q
What are the 4 interactions between amino acid side chains?
A
- Electrostatic interactions (ionic)
- Dipole dipole interactions (H bonds)
- Hydrophobic interactions
- Covalent interactions (disulfide)
4
Q
What are electrostatic interactions between?
A
oppositely charged hydrophilic amino acid side chains
5
Q
what are dipole dipole interactions between?
A
hydrogen bonds are formed between two amino acid side chains
6
Q
Where are hydrophobic interactions found?
A
found in interior of globular proteins where water is excluded
7
Q
What are covalent interactions between?
A
two non metals such as disulfide bonds between two cysteine side chains
8
Q
What are the small amino acids? functions?
A
glycine and alanine
-found in places where two polypeptide chains have to come close together
9
Q
branched amino acids? side chains?
A
valine, leucine, isoleucine
-hydrophobic side chains
10
Q
hydroxyl amino acids? functions?
A
serine, threonine
- form H bonds with hydroxyl group
- forms covalent bonds with carbs in glycoproteins and with phosphate in phosphoproteins
11
Q
sulfur amino acids? functions?
A
cysteine, methionine
- hydrophobic
- cysteine weakly acidic
- forms disulfide bonds
12
Q
aromatic amino acids? bonds formed?
A
phenylalanine, tyrosine, tryptophan
- hydrophobic
- tyr and trip can form H bonds
- tyrosine OH group carries covalently bound phosphate group in some phosphoproteins
13
Q
acidic amino acids? functions?
A
glutamate, aspartate
-negatively charged at pH 7
glutamine, asparagine
- not acidic but form strong H bonds
- asp forms strong N glycosidic bond with carbs in some glycoproteins
14
Q
basic amino acids? function?
A
lysine, arginine, histidine
- positive charge on side chain
- pK of His is low
15
Q
proline? function?
A
- nitrogen tied into ring structure
- stiff and angled
- found at bends in polypeptide
16
Q
cause of sickle cell anemia?result?
A
- valine is substituted for glutamic acid at 6th amino acid for both beta chains
- changes in primary and quaternary structures, hemoglobin shape
- lowers O2 concentration
17
Q
7 functions of proteins?
A
- binding- antibodies
- cell structure- strength, ex. collagen
- enzyme catalysis- largest function, lactase
- mechanical support- muscle contraction, actin, myosin
- regulation- behavior or abundance of enzymes, cell process regulation, insulin
- storage- reservoirs for nutrients, store metal ions, ferritin
- transport - delivers specific substances, hemoglobin, myoglobin, across ion channels
18
Q
primary structure of proteins?
A
determine by the DNA of the gene, is the amino acid sequence
19
Q
secondary structure?
A
- alpha helix
- beta pleated sheet
- combination of the two
- provides maximal H bonding in interior of polypeptides
20
Q
silk fibroin?
A
beta pleated sheets alternating glycine and alanine
21
Q
super secondary structure?
A
- random or non repetitive sequences
- organized motifs of secondary structures in a particular geometric arrangement
- presence of alpha helices and beta sheets in a protein give it flexibility
22
Q
tertiary structure? interactions?
A
- folding of secondary structure into 3D shape
- primary sequence determines tertiary
- interactions between side chains guide folding
Four interactions for tertiary structures:
- electrostatic
- H bonds
- hydrophobic
- disulfide
23
Q
Quaternary structure? interactions?
A
-arrangement of more than one polypeptide chain
Three non covalent interactions:
- electrostatic
- H bonds
- hydrophobic
24
Q
homoproteins?
A
- simple proteins
- contain exclusively amino acids
25
heteroproteins?
- conjugated proteins
| - prosthetic group - non protein part
26
Two classes of proteins?
1. Fibrous
| 2. Globular
27
3 examples of fibrous proteins?
1. keratin
2. collagen
3. elastin
28
Fibrous proteins properties? amino acids? structure?
- water insoluble
- Ala, Val, Leu, Lle, Met, Phe
- single repeating elements of secondary structure
- rope like proteins
- contractile properties
29
2 examples of globular proteins?
- heme
| - myoglobin
30
Globular proteins properties?
- water soluble
- hyrdophilic
- stable structures (3D), complex interactions
- variety of globular protein structures
31
Keratin? properties?
- fibrous
- main constituent of structures that grow from skin
- mechanically durable
- chemically unreactive
- occurs in all higher vertebrates
- glycine and alanine
32
Keratin deficiencies?
-loss of skin integrity, loss of hair, brittle nails
Epidermolysis Bullosa Simplex
- blister formation in epidermis caused by defects in keratin filaments
- Mutations in KRT5 or KRT14 gene
Monilethix
-autosomal dominant hair disease, beaded hair
33
Collagen? where found? properties?
- fibrous
- found in extracellular matrix (ECM)- gives support to cells, cell attachments, strength
- cartilage, tendons, bones, teeth, skin, blood vessels
- vitreous humor of eye, cornea
34
What other ECM proteins does collagen interact with?
- proteoglycans- sugar chain around protein core
| - integrin- bound in cell membrane
35
nascent peptide?
- collagen
| - high glycine and proline/hydroxyproline content
36
pro collagen?
- cells secrete collagen as this precursor form
| - processed by proteolysis of staggered ends leading to cleavage of pro collagen to form Tropocollagen
37
Tropocollagen?
- triple helix is basic unit of collagen
| - formed be cleavage of staggered ends, assembly, and cross linking out of cell
38
what is cross linking important for with collagen?
- achieves tonsil strength necessary for function of connective tissue
- stability
39
How are collagen fibrils formed?
by covalently cross linked via Lysyl Oxidase
40
What leads to further strengthening of collagen?
extensive H bonds using carbonyl and amine of Gly
41
What vitamin is needed for proper collagen formation?
C (ascorbic acid)
42
Collagen diseases?
Scurvy
- ascorbic deficiency, lack of hydroxylation
- collagen not cross linked, decreased strength
- capillary insufficiency
- bruises on limbs and swollen gums, bleed, teeth fall out
Ehlers-Dalos Syndrome
- Cutis hyperelastica
- inherited defects of synthesis of types 1, 3, 5 collagens
- deficiency in collagen processing enzyme
- reduced tensile strength of skin, very stretchy
- loos joints, bruise easily, fragile
Osteogenesis Imperfecta (OI)
- brittle bone syndrome
- can be mild, severe, extremely severe, undefined
- autosomal dominant disease
- glycine is replaced by other amino acids in gene of type 1 of pro collagen, impaired formation of triple helix in ER
43
clinical symptoms of OI?
- blue tint to whites of eyes
- early hearing loss
- weak bones susceptible to fractures
- loose joints (hyper mobility) and flat feet
- some have poor teeth
- bowed legs and arms
- kyphosis
- scoliosis
- humped back
- retarded wound healing
44
Elastin? where found?
- fibrous, elastic
- protein located in connective tissue
- rubber band like, not high tensile strength
- lungs, ligaments, arteries, tendons
- stretch and recoil
- insoluble
- irregular amino acid structure (Gly, Ala, Val, with some Lys, Pro)
- random coil structure
- demosine- unique crosslinks (4 Lys connected at side chains)
45
Disorders of Elastin degradation?
1. alpha-1 antitrypsin antitrypsin deficiency
2. Marfan syndrome
3. Cutis Laxa
46
alpha-1 antitrypsin deficiency? symptoms?
- this protein normally inhibits proteolytic enzymes that degrade elastin in lungs and other tissues (elastase)
- deficiency leads to degradation of elastin
- emphysema
- cirrhosis in liver
- smokers are at risk
47
Marfan syndrome? symptoms?
- autosomal dominant
- degenerative disorder of connective tissue
- tall, long limbs, long fingers
- affects eyes, heart, blood vessels, skeletal system
- defects of heart valves and aorta
- no strenuous activity allowed
48
Cutis Laxa (CL)? symptoms?
- rare, inherited connective tissue disorder
- skin becomes inelastic and hangs loose, internal organs frequently involved
- heterogeneity (autosomal dominant, recessive, X linked)
- serine to proline amino acid substitute
49
what are the proteins in cell membranes?
Globular proteins:
1. integral membrane proteins
2. peripheral membrane proteins
3. glycoproteins
50
Functions of cell membrane proteins?
- constitute about 25% of all proteins
- cell communication to outside world
- transport molecules in or out of cells
- cell recognition, receptors, cell to cell communication
- energy metabolism
- amino acid side chains are non polar
- Ala, Val, Leu, Lle, Phe
51
Function of integrins?
- penetrate hydrophobic regions of bilayer
| - transport
52
Examples of integral membrane proteins?
1. hormone receptors (N linked oligosacc)
2. membrane transporters (Na-K ATPase, ABC transporter, Glucose transporters)
3. ion channels and gates
4. histocompatibility antigens
5. certain enzymes of electron transport chain
6. Gap junction proteins
53
What do all membrane transporters contain?
transmembrane domain which consists of hydrophobic (within membrane) amino acids and hydrophilic amino acids
54
Function of Na-K ATPase?
- some cells use gradient to facilitate transport of glucose and amino acids
- nerve cell electrical impulsion
55
ABC transporters function?
- nutrient uptake
- protein, drug and antibiotic excretion
- osmo regulation
- antigen presentation
- signal transduction
-use energy of ATP hydrolysis to transport across cell membranes
56
Common features of ABC transporters?
- consensus ATP binding domain
- transmembrane domain
- or integral membrane consists of alpha helices, embedded in bilayer
57
Examples of ABC transporters?
1. ion transporters (CFTR)
2. cholesterol transporters (ABCA1)
3. transporters of bile acids
4. transporters of drugs
58
Peripheral membrane proteins? attached? example?
- more loosely associated with membrane
- attached noncovalently to protruding integral proteins
- restricted in their movements
- some tethered to cytoskeletal elements like actin microfilaments
- some anchored to collagen
- Cytochrome C in electron transport chain
59
Glycoproteins?
- covalently attached to oligosaccharides
- glycosylated extracellular segments
- often integral membrane proteins (cell-cell)
- contain N terminal signal sequence- direct growing polypeptide chain to ER, Golgi where carb is added to protein
60
Functions of glycoproteins?
- cell surface recognition (other cells, hormones, viruses)
- cell surface antigenicity (blood group antigens)
- membrane receptors (ligand receptor function)
- component of extracellular matrix and mucins (human gastric glycoproteins)
61
Oxidoreductases?
transfer electrons from a donor (reducing agent) to acceptor (oxidizing agent)
62
transferases?
transfer functional group (amino, phosphate) between molecules
63
isomerases?
rearrange/isomerize molecules
64
lyases?
- synthases
| - add or remove atoms to or form double bond
65
ligases?
- synthetases
| - form bonds with hydrolysis of ATP
66
hydrolases?
cleave bonds via the addition of water
67
examples of oxidoreductase reactions?
1. lactate dehydrogenase (NADH and NAD)
| 2. cytochrome P450
68
Lactate dehydrogenase reaction? cofactors? reducing equivalents?
- simple direct oxidation reduction
cofactors: NAD+ as acceptor, NADH as donor, NADP,+ FAD+
reducing eq:
-electrons may be transferred as hydrogen proton with its electron (H- atom) or hydride ion (H with extra electron)
69
Cytochrome P450 reaction?
-complex and indirect series of oxidation reductions
P450:
- absorbance of proteins at 450nm when bound to CO
- CYP family- heme containing
- acts with other enzymes such as cytochrome P450 reductase, cofactors NADPH as electron donor, flavoprotein
-genetics of P450 enzymes have wide spread implications for drug reactions, CYPs are responsible for metabolizing 1/3 to 1/2 of drugs today
70
What is the overall enzymatic chemical transformation of P450?
hydroxylation where the substrate may be a steroid, fatty acid, drug, or other chemical with a site of oxygenation
71
Where are cytochromes found?
found embedded in the membranes of the smooth ER, microsome, and mitochondria
72
What are some examples of transferases and hydrolases? why are they important? common amino acid targets?
- kinases (transferase) and phosphatases (hydrolase)
- important regulating enzymes
- covalent modifications
- most common targets are serine, threonine, tyrosine
- phosphorylation targets amino acids located distant from catalytic site
73
What is Glutathione? functions?
- important tripeptide in metabolism
- contains glutamic acid, cysteine, glycine
- carboxyl side chain is part of backbone peptide structure
- protect cells from oxidizing agents which react with SH of Cys of glutathione
- antioxidant defense, reduces H2O2
- assists in transport of certain amino acids across membranes
74
Where is the information required for proper protein folding located?
primary structure of peptide
75
What interactions determine how a protein folds?
interactions between side chains of amino acids
76
What agents denature proteins?
- change in pH
- heat
- organic solvents (urea)
- mechanical mixing
- strong acids or bases
- detergents
- ions of heavy metals
77
What could denaturation cause?
causes permanent unfolding and disruption of protein structure
78
Protein chaperones?
- heat shock proteins
- required for proper folding of many proteins
- keep proteins unfolded until biosynthesis is complete
- act as catalysts in folding process, increasing rate
- others protect against tangling
79
What characterizes proteins misfolding?
1. many protein misfolding diseases are characterized by absence of a key protein because it has been eliminated by cell machinery
2. many protein misfolding diseases characterized by its deposition in insoluble aggregates within the cell
80
What diseases are caused by a lack of particular functioning protein due to degradation?
- cystic fibrosis (misfolded CFTR)
- marfan syndrome (misfolded fibrillin)
- Fabry disease (misfolded alpha galactosidase)
- Gauchers disease (misfolded beta glucocerebrosidase)
- retinitis pigmentosa 3 (misfolded rhodopsin)
- some cancers (inactive tumor suppressor)
- Marfan Syndrome (misfolded fibrillin)
- Osteogenesis Imperfecta (misfolded procollagen)
81
What diseases are caused by protein aggregation?
- alzheimers (deposits of amyloid beta and tau)
- type 2 diabetes (deposits of amylin)
- parkinsons (deposits of alpha synuclein)
- creutzfeldt-jakob (deposits of prions)
- hereditary transthyretin amyloidosis (heart failure)
82
What is amyloidoses?
- formation of abnormal long fibrillar protein with mainly beta pleated sheets called amyloid, insoluble aggregates form
- alzheimers
83
Cause of prion disease?
- infectious prion proteins form insoluble aggregates of fibrils
- TSE
- creutsfeldt-jakob disease in humans
- scrapie in sheeps
- mad cow disease in bovine
