BAHAN KULIAH BIOKIMIA POWER POINT BAGIAN 1 /BIOCHEMISTRY POWER POINT LECTURES PART 1 | Karya Tulis Ilmiah

Protein Structure
Lecture 2/26/2003

Protein Structures
A study in the structure-function of proteins.
Amino acid sequence dictates function.
Structures are not “static” but breath and vibrate
Protein dynamics (movement) can be linked to
function

Globular proteins = enzymes and catalysts
Fibrous proteins = structural or connective role.
Structure - function relationships
Some residues and chains are just disordered
“Floppy” flexible which maybe required for
function

Fibrous (structural) proteins 
Keratin 
Nails, hair, horns and feathers
 or  forms

30 variants, tissue specific 
type I            and             type II
acidic negative charge        basic positive charge
 keratin ­ 
•  hair­ 20 M diameter
•  macrofibril 2000 Å parallel to hair 
•  microfibril 80 Å and high sulfur cement protein.

 keratin proteins are helical 
but spacing differs from an  helix
 a 5.1 Å vs. 5.4 Å pitch.  
This change in pitch forms closely associated pairs of 
helices. Each pair consists of a  type I and type II 
protein
Left­handed coil 
 coiled­coil
310 AA residues 7­residue pseudo repeat.
Helical wheel ­ Look down an  helix and residues 
stick out from center of helix 3.6 residues/turn 360 = 
100 per residue

3.6
a ­ b ­ c ­ d ­ e ­ f ­ g  a      repeat on side of helix
                                    

Helical wheel diagram
a and d residues are
nonpolar.

Protofilaments
antiparallel strands

a ­ d are non­polar and face the same side of helix.  
3.6 residues/turn
3.5 residues hydrophobic repeat
The hydrophobic strip aligns between two helices with 
18 inclination from one to another.
They fit well together
Dimer  protofilament  microfibril  macrofibril  hair
 keratin rich in cys and forms disulfides
 hard keratin cys content is high

 soft keratin cys content is cyst low
Perms reduce R­S­­­S­R bonds to    2R­SH  
Curly hair has more Cys residues.

Protein helices are stretchy and can elongate
When keratin is stretched it can form a more sheet like
structure.

keratin of feathers and nails are extended and have a
more rigid and stiff consistency
epidermolysis bullosa simplex and epidermolytic
hyperkeratosis are keratin related diseases involved in
the loss of mechanical integrity of the shin.

Silk Fibroin a  pleated sheet
From spider and insect webs, cocoons, nests and egg sacks.
An almost fully extended  sheet that cannot stretch and is 
strong.
This is why spiderman can support his weight on the web material!!

Fibroin and sericin = web
                      

 sericin  is an amorphous gummy protein
Adult moths dissolve (hydrolyze) their cocoons by cocoonase, this 
digests sericin, clothmoths do the same.
Boiling water also removes sericin and leaves fibroin or silk.

Extended parallel  sheets of (­Gly­Ser­Gly­Ala­Gly­Ala­)N 
Ala from one sheet interdigitates with Ala from another sheet
Silks from different species have different interdigitating 
groups and have differing physical properties.

Silk fibers are strong when extended but cannot be stretched
because of the fully extended sheet form of fibroin

Collagen ­ Triple helical cable
Bones, teeth, cartilage, tendon, ligament, blood vessels 
and skin matrix 

Strong, flexible, stretchy
Several types

I

[1 (I)]2  2I     skin, bone tendon, cornea vessels

II

1 (II)3

      cartilage

III

[1 (III)]3

       vessels, fetal skin

Type I

285 kDA

14A wide

1/3 Gly 15­30% ­4­Hydroxyproline  (Hyp) some 5­Hydroxylysyl 
(Hyl)
4­Hydroxyprolyl
(4­Hyp)
C
N
1
H3C 5

OH

CH

2
4

C

3CH2

H

 

3­Hydroxyproylyl
(3­Hyp)
C
N
1
H3C 5

H

CH

2

3C
4
C
H

H
OH

Gly­X­Y   X often Pro    Y often Hyp 
like a poly Gly or poly Pro helix
Left­handed 3.0 residues/turn pitch 9.4 extended 
conformation the prolines avoid each other.
3 left handed helices combine in a triple rt handed 
coil.

Rope twist or metal cable 
longitudinal force (pulling) is 
supported by lateral 
compression opposite twisted 

strands prevents twists from 
pulling out.

Collagen helices are 
organized into fibrils.
689 A hole repeat
100 ­ 2000 A diameter 
different types make different 
arrays dark us light areas on 
fibril
Hydrophobic repulsion drives 
fibril formation possible Van 
der Waals attraction due to 
packing.
Collagen is 0.4  12% 
carbohydrate (linked sugars)

Vitamin C is required for hydroxyproline formation
Hydroxyproline gives collagen stability and strength by H­
bonding.

Without prolyl hydroxylase collagen denatures at 24C 
instead of 39 to form gelatin.
Scurvy­skin lesions, broken blood vessels, wounds don’t 
heal, teeth fall out, one cannot stand.