Asam Amino dan

Protein
Asam Amino
 Struktur asam amino secara umum adalah satu atom C yang
mengikat empat gugus: gugus amina (NH2), gugus karboksil
(COOH), atom hidrogen (H), dan satu gugus sisa (R, dari
residue) atau disebut juga gugus atau rantai samping yang
membedakan satu asam amino dengan asam amino lainnya

 Asam amino biasanya diklasifikasikan berdasarkan sifat kimia

rantai samping tersebut menjadi empat kelompok; asam
lemah, basa lemah, hidrofilik jika polar, dan hidrofobik jika
nonpolar
 Karena atom C pusat mengikat empat gugus yang berbeda, maka
asam amino memiliki atau karbon asimetrik dan optik aktif
kecuali glisin.

 Pada pH tertentu yang disebut titik isolistrik, gugus amina pada

asam amino menjadi bermuatan positif (terprotonasi, –NH3+),
sedangkan gugus karboksilnya menjadi bermuatan negatif
(terdeprotonasi, –COO-). Titik isolistrik ini spesifik bergantung
pada jenis asam aminonya. Dalam keadaan demikian, asam amino
tersebut dikatakan berbentuk zwitter-ion/ampoter
 Asam amino dapat diGolongkan Berdasarkan Gugus R
 Gugus R Non Polar Gugus R Polar, tidak bermuatan
Alanin asparagin
Isoleusin sistein
Leusin glutamin
Metionin glisin
Fenilalanin serin
Prolin treonin
Triptopan tirosin
Valin

Gugus R bermuatan negatif Gugus R bermuatan positif

Asam aspartat arginin
Asam glutamat histidin
Lisin
Asam amino non dan esensial
essential
essential non-essential semi-essential
precursor
histidine alanine
isoleucine aspartic acid asparagine
leucine glutamic acid glutamine
lysine arginine
methionine cysteine glycine
phenylalanine tyrosine proline
threonine serine
tryptophan
valine
Peptide Bond Formation
(a Condensation Reaction)

A dipeptide
For example, a pentapeptide:
 Amino acid polymers are called…

 Di-, tri-, tetra-, pentapeptides, etc., or

 Generically, peptides or oligopeptides
(up to 30 or so long)
 Bigger ones are called polypeptides (up
to about 100), or
 Proteins, from 70-ish on up
 Their sequences are always written
from the amino-terminus towards the
carboxy-terminal residue (left to right)
Oxytocin vs. Vasopressin
Fungsi protein
 Enzim, lebih dari 2000 jenis eenzim dapat mengkatalisis
reaksi kimia yang berbeda( tripsin, ribonuklease)
 Protein transport; Hb, lipoprotein, mioglobion,
 Protein nutrien dan penyimpanan; gliadin, ovalbumin,
kasein, feritin
 Protein kontraktil atau motil; aktin, miosin, tubulin
 Protein struktural; keratin, fibroin, kolagen, elastin,
proteoglikan
 Protein pertahanan; antibodi, fibrinogen, trombon,
toksin, bisa ular
 Protein pengatur; insulin, hormon,
But most proteins are bigger…

And may be
helped by
oligomerization
____________
Homodimer
Heteropentamer
Dodecamer
Protein Konjugasi
Struktur protein
 The primary structure of a protein is
defined as the complete amino acid
sequence of that protein
Proteins with similar functions often
have similar sequences…
Species variation in cytochrome c

Invariant and Conservative Substitutions

Nonconservative are unshaded
X = trimethyl lysine
And are
evolutionarily
related…

Numbers are the

number of residues
by which each
cytochrome c differs
from its ancestor
The cis configuration of proline is
found frequently in b-turns

_
Struktur Sekunder
 Struktur primer yang melipat satu kali,
membentuk
Two Common Types of b-Turn

behind
In front

•A hydrogen bond spans aa1 and aa4

•The peptide linkage is flipped 180o in I vs. II
•Gly is the only possible aa at position 3 in Type II
 Whenever a bend is introduced…

The strands that enter and leave the bend

must be antiparallel…
Which may form a two-stranded
secondary structure called a b-ribbon
 In which hydrogen bonds form straight
across between the two strands, NH---O=C
 Where adjacent pairs of aa sidechains
alternate projecting above and below the
plane of the b-ribbon
 Which has a slight righthand twist
 And which if continued, becomes a multi-
stranded antiparallel b-sheet
Antiparallel b-Sheet

Note:
1. H-bonds
2. R-groups
3. Pleated character,
most extended
4. R1-R3 distance
0.7 nm 5. b-bends connect
6. strands, ave. = 6
7. Ave. strand length
is about 6 aa’s
Parallel b-Sheet

Note:
1. H-bonds distorted
2. R-groups
3. Pleated character
4. R1-R3 distance
5. Connected by RH
crossover
6. Usually has more
0.65 nm than 5 strands
7. Ave. strand length
is about 6 aa’s
Sidechain Residues Alternate Above
and Below b-Sheets

Antiparallel
b-Sheet

Parallel b-Sheet
Features of b–structures
 The backbone is in its most extended form
 With 2 or more strands, a “pleated” structure is
formed (ribbon or sheet)
 Hydrogen bonding between adjacent strands is a
major contribution to stability
 The R-groups protrude outwards from the peak
of each pleat
 Along each strand, they alternate in pointing
“up” and “down”
Helices Allow More Compact Structures
than Sheets

 They exploit maximum H-bonding within

strands, using nearby groups
 Except proline per se
 May be either right or left handed
Possible Types of Helix
 H-bonds occur between C=O and H-N, r
residues farther along the chain

 forbidden r=2
 rare r=3 long & thin
 common r=4 just right!
(a-helix)
 rare r=5 short & fat
(p-helix)
A Look at the a-Helix: Ball and Stick
C-terminus

N-terminus
The a-helix
 Most common (about 25% of the amino
acids in proteins are in this structure)
 Stability is greatly enhanced by internal
van der Waals contacts
 H-bonds are in-line, optimum distance
 R-groups project outward, and provide
the main constraints on helical structure
R-Group Constraints on a-Helical
Structure

 Proline is a “helix breaker”, and forces a

bend in any a-helix
 Adjacent residues of like charge prevent
helix formation (by repulsion and H-
bond destabilization)
 High glycine content favors alternate
structures instead
 Bulky residues destabilize sterically
The a-Helical Wheel:
Ball and Stick – End View
3
7
4

2 9 8
5 1
The a-Helix:
Space Filling
Models
1
Arg100
Note 4
5
Repeat 7
Distances 8

11
12 Asp103
A Large Fraction of Protein Structure
is a-Helix or b-Sheet

- Fig. 6-18c

Fig. 4-18

- Fig. 4-16
Appreciate the Occurrence Probabilities of
Different Amino Acids
Tertiary Structure: Building a Protein
 Secondary Structural Elements
 Turns and loops
 Ribbons and sheets
 Helices
 Random coil connectors
 Covalent links
 Disulfide bonds
 Prosthetic Groups (sometimes)
 Non-covalently bound molecules
 Coordinated of metal ions
 Prosthetic Groups (sometimes)
Klasifikasi Protein Berdasarkan Bentuk
1. Protein Serat (Fibrous)

In general, fibrous proteins are

- built up from a single element of secondary structure
- insoluble in water (lots of hydrophobic residues)
- involved in structural roles within the cell
Hair is Made of a-Keratin
Right-hand

Left-hand
Fibrous Proteins: a-Keratin
 Hair
 Long, strong
 Wool
 Disulfide links
 Nails
between a-helices
 Claws
 2 a-helices in super-
 Horns
 Skin
twisted coils
Some Helices Can Be Left-Handed!
 Proline is bad for right-handed helices
 Polyproline, however, can form a left-
9C handed helix with 3 residues/turn, and a
pitch of 9C
 Modification to hydroxyproline allows the
formation of hydrogen bonds, and
further stabilization of this unusual
helical form, in collagen…
 This post-translational modification
requires vitamin C as a co-substrate for
3 enzymes that are involved in the
hydroxylation of both proline and lysine
Collagen
 Left-hand single helix, 3
residues/turn
 1/3 Gly, 1/5 Pro or Hyp
 Triplet Gly-X-Pro (or Gly-X-
Hyp) repeats
 Supertwisted coiled coil is
right-handed, made of 3 left-
handed a-chains

LH RH
Stronger than steel!
Collagen Fibrils Are Built Up
From the Triple Superhelices
 The monomer is ~ 1000 aa
 In the triplex, each may be
different in sequence
 Crosslinking of the triplexes
(via unusual aa-links) gives
more strength (but also
more brittleness, with age)
 Alignment is also tissue-
specific, and may vary in
cartilage, bone matrix,
tooth dentin, skin, tendon,
and connective tissue (e.g.
lungs)
Fibrous Proteins: Collagen

 Left handed helix, 3

 Tendons residues per turn
 Cartilage  Gly-X-Pro or Gly-X-Hyp
 Supertwisting of 3
 Bone matrix
strands (not 2)
 Cornea of the eye  “unusual covalent
 Lungs crosslinks”
 Glycine is critical
Fibrous Proteins: Fibroin

 β-sheets
 Silk  Lots of Gly and Ala
 Spider web  No covalent
crosslinking like
keratins (cysteine) or
collagens (“unusual”)
 H-bonding provides
crosslinks
2. Globular Proteins
 Enzymes
 Compact
 Transporters
 Made up of regions of
 Regulatory proteins α-helix, β-sheets, β-
 Immunoglobulins turns, and others as
 Capsid proteins well
 Etc….  Stability results from
“hydrophobic” core
and disulfide bridges
 One Nice, Simple, Globular Protein
is Myoglobin
 A small protein (153 aa’s, 16.7 kD)
 With a heme prosthetic group, so it can
 Bind oxygen in muscle cells
 It is mostly a-helix (78% of its aa’s are in
the 8 segments, from 7 to 23 aa’s long),
linked by turns (some of them b)
 Much of its stability comes from
hydrophobic interactions
Myoglobin Ribbon Structure:
Displays Backbone But No Side Chains
Myoglobin
To understand protein versatility,
you must understand protein structure

o 2o
1 3o 4o
Sintesa Protein ( lanjut..)