PROTEIN

PROTEIN

Oleh :DEDES AMERTANINGTYAS, S.Pt.,MP

PROTEIN

• Elements: C, H, O, N, and sometimes S.• Function: Enzymes, structural proteins,

storage proteins, transport proteins, hormones, proteins for movement, protection, and toxins.

General Structure

• Proteins are made from several amino acids, bonded together. It is the arrangement of the amino acid that forms the primary structure of proteins. The basic amino acid form has a carboxyl group on one end, a methyl group that only has one hydrogen in the middle, and a amino group on the other end. Attached to the methyl group is a R group.

General Structure• Proteins are made from several amino

acids, bonded together. It is the arrangement of the amino acid that forms the primary structure of proteins.

• The basic amino acid form has a carboxyl group on one end, a methyl group that only has one hydrogen in the middle, and a amino group on the other end.

• Attached to the methyl group is a R group.

General Structure

There are 20+ amino acids, each differing only in the composition of the R groups. An R group could be a sulfydrl, another methyl, a string a methyls, rings of carbons, and several other organic groups. Proteins can be either acidic or basic, hydrophilic or hydrophobic. The following table shows 20 amino acids that common in proteins.

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

Amino acid: Basic unit of protein

COO-NH3+ C

R

HAn amino

acid

Different side chains, R, determin the properties of 20 amino acids.

Amino group Carboxylic acid group

20 Amino acids

Glycine (G)

Glutamic acid (E)Asparatic acid (D)

Methionine (M)

Threonine (T)Serine (S)

Glutamine (Q)

Asparagine (N)

Tryptophan (W)Phenylalanine (F)

Cysteine (C)

Proline (P)

Leucine (L)Isoleucine (I)Valine (V)

Alanine (A)

Histidine (H)Lysine (K)

Tyrosine (Y)

Arginine (R)

White: Hydrophobic, Green: Hydrophilic, Red: Acidic, Blue: Basic

Proteins are linear polymers of amino acids

R1

NH3＋ C CO

H

R2

NH C CO

H

R3

NH C CO

H

R2

NH3＋ C COO ー

H＋

R1

NH3＋ C COO ー

H＋

H2OH2O

Peptide bond

Peptide bond The amino acid

sequence is called as primary structure A AF

NG GS T

SD K

A carboxylic acid condenses with an amino group with the release of a water

Amino acid sequence is encoded by DNA base sequence in a gene・

CGCGAATTCGCG・

・GCGCTTAAGCGC・

DNA molecule

＝

DNA base sequence

Amino acid sequence is encoded by DNA base sequence in a gene

Second letterT C A G

First letter

TTTT Phe TCT

Ser

TAT Tyr TGT Cys T

Third letter

TTC TCC TAC TGC CTTA Leu TCA TAA Stop TGA Stop ATTG TCG TAG TGG Trp G

CCTT

Leu

CCT

Pro

CAT His CGT

Arg

TCTC CCC CAC CGC CCTA CCA CAA Gln CGA ACTG CCG CAG CGG G

AATT

IleACT

Thr

AAT Asn AGT Ser TATC ACC AAC AGC CATA ACA AAA Lys AGA Arg AATG Met ACG AAG AGG G

GGTT

Val

GCT

Ala

GAT Asp GGT

Gly

TGTC GCC GAC GGC CGTA GCA GAA Glu GGA AGTG GCG GAG GGG G

Gene is protein’s blueprint, genome is life’s blueprint

Gene

GenomeDNA

Protein

Gene GeneGene

GeneGeneGeneGeneGene

GeneGeneGeneGene

GeneGene

Protein ProteinProtein

ProteinProtein

ProteinProtein

Protein

ProteinProtein

Protein

ProteinProtein

Protein

Gene is protein’s blueprint, genome is life’s blueprint

Genome

Gene GeneGene

GeneGeneGeneGeneGene

GeneGeneGeneGene

GeneGene

Protein ProteinProtein

ProteinProtein

ProteinProtein

Protein

ProteinProtein

Protein

ProteinProtein

Protein

Glycolysis network

3 billion base pair => 6 G letters &

1 letter => 1 byteThe whole genome can be

recorded in just 10 CD-ROMs!

In 2003, Human genome sequence was deciphered!• Genome is the complete set of genes of a living thing.

• In 2003, the human genome sequencing was completed.• The human genome contains about 3 billion base pairs.• The number of genes is estimated to be between 20,000 to 25,000.• The difference between the genome of human and that of

chimpanzee is only 1.23%!

Each Protein has a unique structure

Amino acid sequence

NLKTEWPELVGKSVEEAKKVILQDKPEAQIIVLPVGTIVTMEYRIDRVRLFVDKLDNIAE

VPRVGFolding!

Basic structural units of proteins: Secondary structure

α-helix β-sheet

Secondary structures, α-helix and β-sheet, have regular hydrogen-bonding patterns.

Three-dimensional structure of proteins

Tertiary structure

Quaternary structure

Hierarchical nature of protein structure

Primary structure (Amino acid sequence)↓

Secondary structure （ α-helix, β-sheet ）↓

Tertiary structure （ Three-dimensional structure formed by assembly of secondary structures ）

↓Quaternary structure （ Structure formed by more

than one polypeptide chains ）

Close relationship between protein structure and its function

enzyme

A

B

A

Binding to A

Digestion of A!

enzyme

Matching the shape to A

Hormone receptor AntibodyExample of enzyme reaction

enzyme

substrates

Protein structure prediction has remained elusive over half a century

“Can we predict a protein structure from its amino acid sequence?”

Now, impossible!

Protein Classification• Proteins can be described as having several layers of structure. At the lowest level,

the primary structure of proteins are nothing more that the amino acids which compose the protein, and how those proteins are bonded to each other. The bonds between proteins are called peptide bonds, and they can have either single bonds, double bonds, triple bonds, or more holding the amino acids into a protein molecule.

• At the next level, the secondary structure of proteins, proteins show a definite geometric pattern. One pattern that the protein can take is a helical structure, similar to a spiral staircase. Hair has such a secondary structure. When examined closely, you can see the turns in the proteins of hair molecules. A second geometric pattern is the pleated sheet, where several polypeptide chains go in several different directions. I think of a sheet of paper, or a length of fabric. When viewed closely, silk fibronin, the silk protein, forms such a shape. Skin, although made of more than just proteins, provides another example of a protein with a sheet structure. The following figure shows the pleated sheet secondary structure of silk.

Contoh struktur protein

• Skin fibroin

• Next, we find a tertiary structure to proteins. Here, we find the three-dimensional structure of the globular proteins, where disulfide bridges puts kinks and bends in the secondary structure. Again thinking about hair, some people have straight hair, some have wavy hair, and some have curly hair. The kinks and bends in the secondary structure causes the curls in hair. Curly hair has more kinks and bends that wavy hair, and straight hair has very few, if any bends


• Psoriasin

• At the last, we see the quaternary structure of proteins. This the the form taken by complex proteins formed from two or more smaller, polypeptide chains. The polypeptide chains form pieces of a jigsaw puzzle, that when put together form a single protein. Hemoglobin provides a good example, being made from four polypeptide chains.


• Hemoglobin

PENJELASAN STRUKTUR DAN FUNGSI PROTEIN

Protein Function in Cell

1. Enzymes • Catalyze biological reactions

2. Structural role• Cell wall• Cell membrane• Cytoplasm

Protein Structure

Model Molecule: Hemoglobin

Hemoglobin: Background

• Protein in red blood cells


• Protein in red blood cells• Composed of four subunits, each

containing a heme group: a ring-like structure with a central iron atom that binds oxygen

Red blood cell

Heme Groups in Hemoglobin


• Protein in red blood cells• Composed of four subunits, each

containing a heme group: a ring-like structure with a central iron atom that binds oxygen

• Picks up oxygen in lungs, releases it in peripheral tissues (e.g. muscles)

Hemoglobin – Quaternary Structure

Two alpha subunits and two beta subunits(141 AA per alpha, 146 AA per beta)

Hemoglobin – Tertiary Structure

One beta subunit (8 alpha helices)

Hemoglobin – Secondary Structure

alpha helix

Structure Stabilizing Interactions

• Noncovalent– Van der Waals forces (transient, weak electrical

attraction of one atom for another)– Hydrophobic (clustering of nonpolar groups)– Hydrogen bonding

Hydrogen Bonding

• Involves three atoms: – Donor electronegative atom (D)

(Nitrogen or Oxygen in proteins)– Hydrogen bound to donor (H)– Acceptor electronegative atom (A) in close

proximity

D – H A

D-H Interaction• Polarization due to electron withdrawal

from the hydrogen to D giving D partial negative charge and the H a partial positive charge

• Proximity of the Acceptor A causes further charge separation

D – H Aδ- δ+ δ-

D-H Interaction• Polarization due to electron withdrawal from the

hydrogen to D giving D partial negative charge and the H a partial positive charge

• Proximity of the Acceptor A causes further charge separation

• Result:– Closer approach of A to H– Higher interaction energy than a simple van der Waals interaction

D – H Aδ- δ+ δ-

Hydrogen BondingAnd Secondary Structure

alpha-helix beta-sheet

Structure Stabilizing Interactions

• Noncovalent– Van der Waals forces (transient, weak electrical

attraction of one atom for another)– Hydrophobic (clustering of nonpolar groups)– Hydrogen bonding

• Covalent– Disulfide bonds

Disulfide Bonds• Side chain of cysteine contains highly reactive

thiol group

• Two thiol groups form a disulfide bond

Disulfide Bridge

Disulfide Bonds• Side chain of cysteine contains highly reactive

thiol group

• Two thiol groups form a disulfide bond• Contribute to the stability of the folded state by

linking distant parts of the polypeptide chain

Protein :

Disulfide Bridge – Linking Distant Amino Acids

Hemoglobin – Primary Structure

NH2-Val-His-Leu-Thr-Pro-Glu-Glu-Lys-Ser-Ala-Val-Thr-Ala-Leu-Trp-Gly-Lys-Val-Asn-Val-Asp-Glu-Val-Gly-Gly-Glu-…..

beta subunit amino acid sequence

Protein Structure - Primary

• Protein: chain of amino acids joined by peptide bonds

Protein Structure - Primary

• Protein: chain of amino acids joined by peptide bonds

• Amino Acid– Central carbon (Cα) attached to: • Hydrogen (H)• Amino group (-NH2)• Carboxyl group (-COOH)• Side chain (R)

General Amino Acid Structure

Cα

H

R

COOHH2N

General Amino Acid StructureAt pH 7.0

Cα

H

R

COO-+H3N

General Amino Acid Structure

Amino Acids

• Chiral

Chirality: Glyceraldehyde

L-glyderaldehydeD-glyderaldehyde

Amino Acids

• Chiral• 20 naturally occuring; distinguishing side

chain

20 Naturally-occurring Amino Acids

Amino Acids

• Chiral• 20 naturally occuring; distinguishing side

chain• Classification:

• Non-polar (hydrophobic)• Charged polar• Uncharged polar

Alanine:Nonpolar

Serine:Uncharged Polar

Aspartic AcidCharged Polar

GlycineNonpolar (special case)

Peptide Bond

• Joins amino acids

Peptide Bond Formation

Peptide Chain

Peptide Bond

• Joins amino acids• 40% double bond character

– Caused by resonance

Peptide bond


– Caused by resonance– Results in shorter bond length

Peptide Bond Lengths

Peptide bond


– Caused by resonance– Results in shorter bond length– Double bond disallows rotation

Protein Conformation Framework

• Bond rotation determines protein folding, 3D structure

Bond Rotation Determines Protein Folding



• Torsion angle (dihedral angle) τ– Measures orientation of four linked

atoms in a molecule: A, B, C, D



• Torsion angle (dihedral angle) τ– Measures orientation of four linked atoms

in a molecule: A, B, C, D– τABCD defined as the angle between the

normal to the plane of atoms A-B-C and normal to the plane of atoms B-C-D

Ethane Rotation

A

CB

DA

B

C

D



• Torsion angle (dihedral angle) τ– Measures orientation of four linked atoms

in a molecule: A, B, C, D– τABCD defined as the angle between the

normal to the plane of atoms A-B-C and normal to the plane of atoms B-C-D

– Three repeating torsion angles along protein backbone: ω, φ, ψ

Backbone Torsion Angles


• Dihedral angle ω : rotation about the peptide bond, namely Cα

1-{C-N}- Cα2



1-{C-N}- Cα2

• Dihedral angle φ : rotation about the bond between N and Cα



1-{C-N}- Cα2

• Dihedral angle φ : rotation about the bond between N and Cα

• Dihedral angle ψ : rotation about the bond between Cα and the carbonyl carbon


• ω angle tends to be planar (0º - cis, or 180 º - trans) due to delocalization of carbonyl π electrons and nitrogen lone pair


• ω angle tends to be planar (0º - cis, or 180 º - trans) due to delocalization of carbonyl pi electrons and nitrogen lone pair

• φ and ψ are flexible, therefore rotation occurs here




• However, φ and ψ of a given amino acid residue are limited due to steric hindrance

Steric Hindrance

• Interference to rotation caused by spatial arrangement of atoms within molecule

• Atoms cannot overlap• Atom size defined by van der Waals radii• Electron clouds repel each other




• However, φ and ψ of a given amino acid residue are limited due to steric hindrance

• Only 10% of the {φ, ψ} combinations are generally observed for proteins

• First noticed by G.N. Ramachandran

Sequence Similarity

• Sequence similarity implies structural, functional, and evolutionary commonality

Homologous Proteins:Enterotoxin and Cholera toxin

Enterotoxin Cholera toxin

80% homology

Sequence Similarity


• Low sequence similarity implies little structural similarity

Nonhomologous Proteins:Cytochrome and Barstar

Cytochrome Barstar

Less than 20% homology

Sequence Similarity


• Low sequence similarity implies little structural similarity

• Small mutations generally well-tolerated by native structure – with exceptions!

Sequence Similarity Exception• Sickle-cell anemia resulting from one residue

change in hemoglobin protein• Replace highly polar (hydrophilic) glutamate

with nonpolar (hydrophobic) valine

Sickle-cell mutation in hemoglobin sequence

Normal Trait• Hemoglobin molecules exist as single,

isolated units in RBC, whether oxygen bound or not

• Cells maintain basic disc shape, whether transporting oxygen or not

Sickle-cell Trait• Oxy-hemoglobin is isolated, but de-

oxyhemoglobin sticks together in polymers, distorting RBC

• Some cells take on “sickle” shape

Sickle-cell

RBC Distortion• Hydrophobic valine replaces hydrophilic glutamate• Causes hemoglobin molecules to repel water and be

attracted to one another• Leads to the formation of long hemoglobin filaments

Hemoglobin Polymerization

Normal

Mutant

RBC Distortion• Hydrophobic valine replaces hydrophilic glutamate• Causes hemoglobin molecules to repel water and be

attracted to one another• Leads to the formation of long hemoglobin filaments • Filaments distort the shape of red blood cells

(analogy: icicle in a water balloon)• Rigid structure of sickle cells blocks capillaries and

prevents red blood cells from delivering oxygen

Capillary Blockage

Sickle-cell Trait• Oxy-hemoglobin is isolated, but de-

oxyhemoglobin sticks together in polymers, distorting RBC

• Some cells take on “sickle” shape• When hemoglobin again binds oxygen,

again becomes isolated• Cyclic alteration damages hemoglobin

and ultimately RBC itself

Protein: The Machinery of Life

“Life is the mode of existence of proteins, and this mode of existence essentially consists in the constant self-renewal of the chemical constituents of these substances.”

Friedrich Engles, 1878

NH2-Val-His-Leu-Thr-Pro-Glu-Glu-Lys-Ser-Ala-Val-Thr-Ala-Leu-Trp-Gly-Lys-Val-Asn-Val-Asp-Glu-Val-Gly-Gly-Glu-…..

PROTEIN

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