Protein

Structure & Function

(Enzyme)

dr. Sri Wulandari, MSc

 Key to Remember
• Chemical bond :
– Covalent bond
– Noncovalent bond :
• electrostatic attractions (ionic bonds)
• hydrogen bonds
• van der Waals attractions
• the hydrophobic force.
Covalent Bond
Covalent Bond...
 Hidrogen Bond
• hydrogen bonds form when a hydrogen atom is
“sandwiched” between two electron-attracting
atoms
• (usually oxygen or nitrogen).
Hydrophilic vs Hydrophobic

Hydrophilic (“water loving”) = polar

Hydrophobic (‘water fearing”) = non polar
Electrostatic Attractions
Van Der Waals Attractions
Hydrophobic Force
PROTEIN STRUCTURE
 Protein
• Proteins are made from a long unbranched
chain of amino acids, each linked by covalent
peptide bonds → polypeptides
• Polypeptide backbone is the repeating sequence
of the N-C-C-N-C-C… in the peptide bond
• Attached to backbone → the side chain
Amino Acids
 Amino Acids...

Hydrophilic Hydrophobic
 Families of Amino Acids
Uncharged
Basic Acidic Nonpolar
Polar

Alanine
Asparagine
Lysine Valine
Aspartic acid Leucine
Glutamine
Isoleucine
Proline
Arginine Serine
Phenylalanine
Methionine
Threonine
Glutamic acid Tryptophan
Histidine Glycine
Tyrosine
Cysteine
 Peptide Bond
Amino acids are commonly joined together by an
amide linkage, called a peptide bond
 Noncovalent Bond

Noncovalent bond helps protein fold

 Protein Folding
• Three dimentional
structure
• Determined by the
order of the amino
acids
• Proteins fold into a
conformation of
lowest energy
• Assisted by molecule
chaperon
 Protein Folding...
• Regular folding pattern :
– α helix
– β sheet

α helix β sheet
 α helix & β sheet
• α helix
– hydrogen bond forms
between 4th peptide bond
• β sheet
– parallel or antiparallel
chain
– hydrogen bonds connect
the peptide bonds
 Protein UnFolding
• Denaturation is the process of unfolding the
protein
– Can be down with heat, pH or chemical compounds
– In the chemical compound, can remove and have the
protein renature or refold
Protein UnFolding...
 Levels of Structure
• Primary structure
– Amino acid sequence
• Secondary structure
– Stretches of polypeptide chain that
form α helices and β sheets
• Tertiary structure
– The full three-dimensional
organization of a polypeptide chain
• Quatenary structure
– a complex of more than one
polypeptide chain
 Protein Subunit
• Larger protein molecules often contain more
than one polypeptide chain (subunits), linked by
noncovalent bond

Hemoglobin
 Protein Domain
• a substructure produced by any contiguous part
of a polypeptide chain that can fold
independently of the rest of the protein into a
compact, stable structure.
• 40 - 350 amino acids
• The different domains are often associated with
different function
• Proteins can have one to many domains
depending on protein size
Protein Domain...

Src protein kinase

PROTEIN FUNCTIONS
 Basic of Protein Function
• All proteins bind to other molecules → ligand
• Binding site – part of the protein that interacts
with the ligand
– Consists of a cavity formed by a specific arrangement
of amino acids
– Binding site-ligan → hand in glove
• Protein – ligand binding depends on a set of
noncovalent bond
Basic of Protein Function
 Basic of Protein Function...
• chemical reactivity depends on :
– which amino acid side chains are expose
– amino acid side chains exact orientation
relative to one another
Classification & Functions
ENZYME
 Enzyme
• Catalyst : a substance that increases the rate of
a chemical reaction without itself undergoing any
permanent chemical change
• Enzyme : a substance produced by a living
organism that acts as a catalyst to bring about a
specific biochemical reaction
• Enzymes speed up reactions → highly specific
catalysts
• Enzyme cause the chemical transformations that
make and break covalent bonds in cells.
 Enzyme...
• Enzyme bind to one or more ligands →
substrates
• Enzyme – substrates → products
• Unchanged after reaction
• Enzyme names typically end in “-ase,”
usually indicates the substrate or product
and the nature of the reaction catalyzed.
Types of Enzyme
 Enzyme Action

Enzyme + Substrate

Enzyme Substrate

Enzyme Product

Enzyme + Product
 Enzyme Action...
• Substrate binding is the first step in enzyme
catalysis

• The transition state : a series of intermediate states of altered

geometry and electron distribution of the substrate molecule
before they form the ultimate products
 Enzyme Action...
• The free energy required to attain the most unstable
intermediate state → activation energy
• Enzymes speed reactions by selectively stabilizing
transition states

Without Enzyme With Enzyme

Enzyme Action...
 Reaction Rates

• Vmax : maximum rate of the reaction

• Turnover number : Vmax divided by enzyme consentration
• KM : substrate consentration that allows reaction to
proceed at ½ Vmax
Lysozyme
Lysozyme...
Strategies Of Enzyme Catalysis
 CoEnzyme
• small molecule or metal atom tightly associated
with enzyme active site that assists with their
catalytic function
 Enzyme Regulation
• Cells regulate enzyme :
– regulating the expression of the gene that encodes
that enzyme
– confining sets of enzymes to particular subcellular
compartments
• distinct membrane-bounded compartment
• protein scaffold
– Proteolysis
– Negative regulation
– Positive regulation
• the accumulation of ADP activates several enzymes involved
in the oxidation of sugar molecules, to convert more ADP to
ATP
 Enzyme Regulation...
• Competitive inhibition occurs when a molecule
similar in size& shape to the substrate competes
with the substrate for access to the active site
• Allosteric regulation occurs when a molecule
causes a change in enzyme shape by binding to
the enzyme at a location other than the active
site → the regulatory site
– Allosteric regulation can activate or deactivate the
enzyme
Enzyme Regulation...
Enzyme Regulation...
 Enzyme Regulation...

Positive Regulation Negative Regulation

 Referensi
• Alberts B, Johnson A, Lewis J, Raff M,
Roberts, Walker P. 2015. The Molecular
Biology of The Cell 6th ed. Garland
Science. UK
 .........Thank
You