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Structural hierarchy of protein

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(1)

Structural hierarchy of protein

(2)

Primary and Secondary Structure

n Primary structure

§ Linear arrangement (sequence) of amino acids

n Secondary structure

§ Local folding of polypeptide chain

§

a helix, b sheet : 60% of the polypeptide chain

§

Random coils and U-shaped turn

n Primary structure

§ Linear arrangement (sequence) of amino acids

n Secondary structure

§ Local folding of polypeptide chain

§

a helix, b sheet : 60% of the polypeptide chain

§

Random coils and U-shaped turn
(3)

a-Helix

§

Hydrogen bond between O (C=O, n) and H (NH, n+4)

§

Side chains point outward

§

a-keratins (hair)

§

Hydrogen bond between O (C=O, n) and H (NH, n+4)

§

Side chains point outward

§

a-keratins (hair)
(4)

Common Hydrogen Bonds

in Biological Systems

(5)

b sheet

n b sheet

§

Zigzag polypeptide backbone

§

Hydrogen bonding between adjacent b strands

§

Parallel or antiparallel

n Amino acids for specific b sheet structure

§

b-keratins (silk fibroin, spider web) : rich in small amino acids (Gly, Ala) n b sheet

§

Zigzag polypeptide backbone

§

Hydrogen bonding between adjacent b strands

§

Parallel or antiparallel

n Amino acids for specific b sheet structure

§

b-keratins (silk fibroin, spider web) : rich in small amino acids (Gly, Ala)
(6)

Protein conformation is stabilized largely by weak interactions

n Conformation

§

Spatial arrangement of atoms in a protein

n Noncovalent interactions determining protein conformation

§

hydrogen bonding within protein

§

Hydrophobic interaction

§

Ionic interactions within protein

n Covalent bond determining protein conformation

§

Disulfide bonds : uncommon

Protein conformation

n Conformation

§

Spatial arrangement of atoms in a protein

n Noncovalent interactions determining protein conformation

§

hydrogen bonding within protein

§

Hydrophobic interaction

§

Ionic interactions within protein

n Covalent bond determining protein conformation

§

Disulfide bonds : uncommon
(7)

Tertiary Structure

n Overall 3D arrangement of a polypeptide chain

n Stabilization

§ weak interaction

§ Hydrophobic interaction between nonpolar side chains

§ Hydrogen bond between polar side chains and peptide bonds

§ Disulfide bond formation

n Overall 3D arrangement of a polypeptide chain

n Stabilization

§ weak interaction

§ Hydrophobic interaction between nonpolar side chains

§ Hydrogen bond between polar side chains and peptide bonds

§ Disulfide bond formation

(8)

Quaternary Structure

§ Arrangement of protein subunits

§ E. coli RNA polymerase : Five polypeptide chains

Bacterial RNA polymerase

(9)

Carbohydrates:

Mono- and Polysaccharides

n (CH

2

O)

n

, C : H : O = 1 : 2 : 1

n Monosaccharide ; Simple sugars

n Disaccharide

§

sucrose (glucose + fructose)

§

lactose (galactose + glucose)

n Polysaccharide

§

pectin, starch, cellulose --- from glucose

§

agar

n (CH

2

O)

n

, C : H : O = 1 : 2 : 1

n Monosaccharide ; Simple sugars

n Disaccharide

§

sucrose (glucose + fructose)

§

lactose (galactose + glucose)

n Polysaccharide

§

pectin, starch, cellulose --- from glucose

§

agar
(10)

Mono- and Disaccharides

OH

(a form)

1 2

a b

1

6 6

4

(a form)

1 a

b

1 4

CH2OH I

(11)

Linear and Ring Structure

n Monosaccharide may be present in the form of a linear or ring structure

n In solution, it is in the form of a ring structure

n Numbering C from the C nearest the carbonyl group

n Monosaccharide may be present in the form of a linear or ring structure

n In solution, it is in the form of a ring structure

n Numbering C from the C nearest the carbonyl group

1

6

No L-glucose exists

(12)

Polysaccharides

n Starch: amylose + amylopectin

n Amylose (a-1,4-Glycosidic linkage)

n Cellulose (b-1,4-Glycosidic linkage)

1 4

n Starch: amylose + amylopectin

n Amylose (a-1,4-Glycosidic linkage)

n Cellulose (b-1,4-Glycosidic linkage)

(13)

Polysaccharides

n Amylopectin (branched chain, a-1,6-Glycosidic linkage)

n Glycogen

§ the main storage polysaccharide of animal cells

§ similar structure to that of amylopectin

1

6

n Amylopectin (branched chain, a-1,6-Glycosidic linkage)

n Glycogen

§ the main storage polysaccharide of animal cells

§ similar structure to that of amylopectin

6

(14)

Roles of Carbohydrates

§ Molecular recognition

§ Often found connected to other molecules on the outsides of cells --- cellular recognition, cell signaling, cell adhesion

§ e.g. blood typing : sugar chains in the membrane of RBC

(15)

Lipids

n Characteristics

§

Water insolubility

§

Diverse structures n Functions

§

Energy storage

§

Fatty acid derivatives (fat)

§

Components of biological membrane

§

Glycerophospholipids, sphingolipids, cholesterol

§

Signals

§

Hormones (steroids, Vitamin D3 (hormone precursor))

§

Enzyme cofactors

§

Vitamin K

§

Pigment

§

Vitamin A

n Characteristics

§

Water insolubility

§

Diverse structures n Functions

§

Energy storage

§

Fatty acid derivatives (fat)

§

Components of biological membrane

§

Glycerophospholipids, sphingolipids, cholesterol

§

Signals

§

Hormones (steroids, Vitamin D3 (hormone precursor))

§

Enzyme cofactors

§

Vitamin K

§

Pigment

§

Vitamin A
(16)

Fat

§

Triacylglycerol

§

glycerol + fatty acid (Ester linkage of glycerol with 3 fatty acids)

§

High energy C-H, C-C bonds à good energy storage
(17)

Physical Properties of Fatty Acids

n Water solubility

§

Longer chain à lower solubility n Melting point

§

Depending on the degrees of packing

§

Length and degree of unsaturation

§

Saturated fatty acid (a, c)

§

Tight packing à high melting point

§

Solid at room temperature

§

Unsaturated fatty acid (b)

§

more double bonds à liquid at room temperature

n Water solubility

§

Longer chain à lower solubility n Melting point

§

Depending on the degrees of packing

§

Length and degree of unsaturation

§

Saturated fatty acid (a, c)

§

Tight packing à high melting point

§

Solid at room temperature

§

Unsaturated fatty acid (b)

§

more double bonds à liquid at room temperature
(18)

Phospholipid

n Glycerol backbone

n two fatty acids (hydrophobic) + phosphate (hydrophilic)

(19)

Cholesterol

§ Component of animal cell membranes : increase membrane fluidity

§ Starting material for steroid hormones and bile

§ Component of animal cell membranes : increase membrane fluidity

§ Starting material for steroid hormones and bile

(20)

Steroids

n Derivatives of sterols

§ Lacking alkyl chain on ring D of cholesterol

§ More polar that cholesterol n Working mechanism

§ Moving through blood stream

§ Bind to receptors in nucleus and activate gene expression and thus metabolism

§ Very high affinity to the receptor

§

Working at less than nanomolar

Steroid hormones

n Derivatives of sterols

§ Lacking alkyl chain on ring D of cholesterol

§ More polar that cholesterol n Working mechanism

§ Moving through blood stream

§ Bind to receptors in nucleus and activate gene expression and thus metabolism

§ Very high affinity to the receptor

§

Working at less than nanomolar

Steroid hormones

(21)

Nucleic Acids, RNA, and DNA

n Nucleotides

§

Building blocks of nucleic acids (DNA or RNA)

§

(deoxy)ribose + phosphate group + base

§

Bases: adenine (A), guanine (G), cytosine (C), thymine (T)

n Terminology

§

Base

§

Nucleoside : sugar + base

§

Nucleotide : sugar + base + phosphate

n Nucleotides

§

Building blocks of nucleic acids (DNA or RNA)

§

(deoxy)ribose + phosphate group + base

§

Bases: adenine (A), guanine (G), cytosine (C), thymine (T)

n Terminology

§

Base

§

Nucleoside : sugar + base

§

Nucleotide : sugar + base + phosphate

o

o

(22)

Nucleotides

Adenine Guanine Cytosine Thymine (D) Uracil (R)

Base Nucleoside

Adenosine Guanosine Cytidine Thymidine Uridine Nucleotide

Adenylate Guanylate Cytidylate Thymidylate Uridylate

Nucleoside Nucleotide

H Adenine Guanine Cytosine Thymine (D) Uracil (R)

RNA DNA

2’-Deoxyribose

Adenosine Guanosine Cytidine Thymidine Uridine

Adenylate Guanylate Cytidylate Thymidylate Uridylate

Purine Pyrimidine

(23)

AMP, ADP, ATP

AMP = Adenylate (cf. dAMP)

OH

OH

OH

(24)

Nucleotide Chains

§ e.g., DNA

§ Linkage of 5’ carbon to 3’ carbon through phosphodiester

bond

(25)

Nucleotide Chains

n e.g., DNA double strand n Base pairing

§

C=G, T=A : hydrogen bonding

§

Complementary base pairs

§

Antiparallel strand in DNA molecule
(26)

DNA Replication

n Synthesis of a complementary strand using the other strand as a template

n DNA polymerase

(27)

Expression of Genetic Information

DNA

Replication

Transcription

mRNA

Protein

Translation

(28)

Cell Nutrients

(29)

Growth media

(30)

Metabolism

(31)

Metabolism

(32)

Bioenergetics

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