protein

Proteins

Proteins
(Greek = “of first importance”)Functions:Structure - skin, bones, hair, fingernailsCatalysis - biological catalysts are enzymesMovement - muscle: actin and myosinTransport - hemoglobin, transport thru membranes

Proteins

Functions: Hormones - insulin, oxytocin, HGH, etc. Protection - antigen-antibody reactions,fibrinogen in clotting Storage - casein in milk, ferritin in liver-stores iron Regulation - control in expression of genes

Proteins

Protein types: 9000 different proteins in a cell Fibrous Protein Insoluble in H2O Used mainly for structural purposes Globular Protein Partly soluble in H2O Usually not used for structural purposes

Proteins are Natural Polymers

Proteins are constructed in the body from many repeating units call amino acidsJust like other polymers the amino acids (monomers) are joined together to make long chains (polymers) – but we call them proteins insteadAll of the polymer information applies to proteins – cross linking, rings, polarity etc.

Amino Acids

The Building Blocks of proteins Contains an amino group and an acid group Nature synthesizes about 20 common AA All but one (proline) fit this formula: AA Proline:

Amino Acids

Amino Acids (AA) The twenty common are Called alpha amino acids One and three letter codes given to 20 common AA All but glycine (where R=H)exist as a pair of enantiomers nature usually produces theL amino acid

Amino Acids

Amino Acids (AA) Sometimes classifiedas AA with: nonpolar R groups polar but neutral R groups acidic R groups basic R groups

Zwitterions

An acid -COOH andan amine -NH2 groupcannot coexistThe H+ migrates to the-NH2 groupCOO- and NH3+ are actually present, calleda “Zwitterion”

Zwitterions

Zwitterion = compound where both a positive charge and a negative charge exist on the same molecule AA are ionic compounds They are internal salts In solution their form changesdepending on the pH
AA’s

Zwitterions

pH = 1-5
excess H+
excess OH-
pH = 10-14
more basic
more acidic
AA’s


Zwitterions
pH = 1-5
excess H+
excess OH-
pH = 10-14
more basic
more acidic
at pI (isoelectric point) charge = 0
AA’s

pI
The pI is the “isoelectric point”The pI is the pH whereNO charge is on the AA: at pI charge = 0
(Not necessarily at a neutral pH)

Amino Acids

The amino acids obtained by hydrolysis of proteins differ in respect to R (the side chain). The properties of the amino acid vary as the structure of R varies.
C
C
O
O
– R
H
H3N
+

Amino Acids

Glycine is the simplest amino acid. It is the only one in the table that is achiral. In all of the other amino acids in the table the a carbon is a stereogenic center.
C
C
O
O
– H
H
H3N
+
Glycine
(Gly or G)

Glycine (Gly or G)

Amino Acids
C
C
O
O
– CH3
H
H3N
+
Alanine
(Ala or A)

Alanine (Ala or A)

Amino Acids
C
C
O
O
– CH(CH3)2
H
H3N
+
Valine
(Val or V)

Valine (Val or V)

Amino Acids
C
C
O
O
– CH2CH(CH3)2
H
H3N
+
Leucine
(Leu or L)

Leucine (Leu or L)

Amino Acids
C
C
O
O
– CH3CHCH2CH3
H
H3N
+
Isoleucine
(Ile or I)

Isoleucine (Ile or I)

Amino Acids
C
C
O
O
– CH2OH
H
H3N
+
Serine
(Ser or S)

Serine (Ser or S)

Amino Acids
C
C
O
O
– CH3CHOH
H
H3N
+
Threonine
(Thr or T)

Threonine (Thr or T)

Amino Acids
C
C
O
O
– CH3SCH2CH2
H
H3N
+
Methionine
(Met or M)

Methionine (Met or M)

Amino Acids
C
C
O
O
– CH2SH
H
H3N
+
Cysteine
(Cys or C)

Cysteine (Cys or C)

Amino Acids
Aspartic Acid
C
C
O
O
– H
H3N
+
OCCH2
O
– (Asp or D)

Aspartic Acid (Asp or D)

Amino Acids
Glutamic Acid
C
C
O
O
– H
H3N
+
OCCH2CH2
O
– (Glu or E)

Glutamic Acid (Glu or E)

Amino Acids
Proline
C
C
O
O
– CH2
H
H2N
+
H2C
CH2
(Pro or P)

Proline (Pro or P)

Amino Acids
Phenylalanine
(Phe or F)

Phenylalanine (Phe or F)

Amino Acids
Tyrosine
(Tyr or Y)

Tyrosine (Tyr or Y)

Amino Acids
Histidine
(His or H)

Histidine (His or H)

Cysteine
The AA Cysteine exists as a dimer:
a disulfide linkage
AA’s


Peptides
AA are also called peptides They can be combined to form...
AA’s

Peptides

AA are also called peptides They can be combined to form a dipeptide.
a peptide bond

Peptides

Known as a “dipeptide” a peptide bond
amine end
acid end
glycylalanine (Gly-Ala), a dipeptide

Peptides

Glycylalanine is not the same as Alanylglycine
glycylalanine
alanylglycine

Peptides

Synthesis of Alanylglycine
alanylglycine

Polar (Hydrophilic) R Groups

Serine (Ser)
Cysteine (cys)
Glutamine (Gln)
Asparagine (Asn)
Tyrosine (Tyr)
Threonine (Thr)
http://www.indstate.edu/thcme/mwking/amino-acids.html

Peptides

Addition of peptides (head to tail) Formation of: dipeptides tripeptides tetrapeptides pentapeptides polypeptides PROTEINS
AA’s

Student Practice

Show the product for the following combination of amino acidsGlu – Pro – His Pro – Asn – Leu Val – Ala – Trp


http://www.youtube.com/watch?v=va0DNJId_CM

Proteins

Proteins usually contain about 30+ AA AA known as residues One letter abbreviations G, A, V, L Three letter abbreviations Gly, Ala, Val, Leu N terminal AA (amine end) on LEFT C terminal AA (carboxyl end) on RIGHT glycylalanine Gly-Ala G-A
AA’s

Polypeptides

Polypeptides
peptide bonds
peptide bonds
side chains
amino acid residues
AA’s

Solubility

Polypeptides or Proteins If there is a charge on a polypeptide, it is more soluble in aqueous solution If there is NO CHARGE (neutral at pI), it is LEAST SOLUBLE in solution
charged
charged

Protein Structure

Primary Structure 1oLinear sequence of AASecondary Structure 2oRepeating patterns ( helix,  pleated sheet)Tertiary Structure 3oOverall conformation of proteinQuaternary Structure4oMultichained protein structure


Protein Structure
Primary Structure 1o Linear sequence of AA
AA 1
AA 2
AA 3
AA 4
AA 5
AA 6
With any 6 AA residues, the number of possible combinations is 6 x 6 x 6 x 6 x 6 x 6 = 46656
AA’s

Protein Structure

Primary Structure
AA 1
AA 2
AA 3
AA 4
AA 5
AA 6
With any 6 of the 20 common AA residues, the number of possible combinations is 20 x 20 x 20 x 20 x 20 x 20 = 64,000,000
(and this is not nearly large enough to be a protein!)
AA’s


Protein Structure
Primary Structure A typical protein could have 60 AA residues. This would have 2060 possible primary sequences.  2060 = 1078This results in more possibilities for this small protein than there are atoms in the universe!

Protein Structure

Primary Structure Sometimes small changes in the 1o structure do not alter the biological function, sometimes they do.
AA’s

Changes and Effect of AA change

Cattle and hog insulin is used for humans but is differentSickle cell anemia – only one change in an amino acid – changes the hemoglobin From yahoo images

youtube

https://www.youtube.com/watch?v=Qd0HrY2NlwY

Protein Structure

Secondary StructureRepeating patternswithin a region Common patterns helix pleated sheetOriginally proposed byLinus PaulingRobert Corey AA’s

Protein Structure

Secondary Structure helixSingle protein chainShape maintained byintramolecular H bondingbetween -C=O and H-N-Helical shape  helix is clockwise AA’s


Protein Structure
Secondary Structure pleated sheetSeveral protein chainsShape maintained byintramolecular H bondingand other attractive forces between chainsChains run anti-paralleland make U turns at ends AA’s

Protein Structure

Secondary StructureRandom CoilsFew proteins haveexclusively  helix or pleated sheetMany have non-repeatingsections called:Random Coils AA’s

Collagen Protein Structure

Secondary StructureTriple Helix of CollagenStructural protein of connective tissuesbone, cartilage, tendonaorta, skinAbout 30% of human body’s proteinTriple helix units = tropocollagen AA’s

Youtube

http://www.youtube.com/watch?v=YmuFI1jtc8M&feature=PlayList&p=C8887E4E7D367515&index=0&playnext=1 http://www.youtube.com/watch?v=gXeYf9dLT3s

Tertiary Structure

The Three dimensional arrangement of every atom in the moleculeIncludes not just the peptide backbone but the side chains as wellThese interactions are responsible for the overall folding of the proteinThis folding defies its functionand it’s reactivity AA’s

Tertiary Structure

The Tertiary structure is formed by the following interactions: Covalent Bonds Hydrogen Bonding Salt Bridges Hydrophobic Interactions Metal Ion Coordination
AA’s

Tertiary Structure –Covalent Bonding The most common covalent bond in forming the tertiary structure is the disufide bond It is formed from the disulfide Interaction of cysteine


Tertiary Structure –Hydrogen Bonding Anytime you have a hydrogen connected to a F O of N – you can get hydrogen bondingThese interactions can occureon the side chain, backboneor both

Tertiary Structure –Salt Bridge Salt bridges are due to charged portions of the protein. Opposite charges will attract and Form ionic bonds Some examples are the NH3+ and COO- areas of the protein

Tertiary Structure –hydrophobic interactions Because the nonopolar groups will turn away from the water and the polar groups toward it, hydrophobic interactions take place. These interactions are strong enough to help define the overall structure of a protein

Tertiary Structure –Metal Ion Coordination Two side chains with the same charge would normally repel each other However, if a metal is placed between them, they will coordinate to the meal and be connected together. These metal coordinations are Important in tertiary structure formation

Tertiary Structure

Quaternary Structure
Highest level of organization Determines how subunit fit together Example Hemoglobin (4 sub chains) 2 chains 141 AA 2 chains 146 AA - Example - Collagen

Denaturation

DenaturationAny physical or chemical agent that destroys the conformation of a protein is said to “denature” itExamples:Heat (boil an egg) to gelatinAddition of 6M Urea (breaks H bonds)Detergents (surface-active agents)Reducing agents (break -S-S- bonds)

Denaturation

Denaturation Examples: Acids/Bases/Salts (affect salt bridges) Heavy metal ions (Hg2+, Pb2+) Some denaturation is reversible Urea (6M) then add to H2O Some is irreversible Hard boiling an egg

Denaturation

Denaturation