Search for notes by fellow students, in your own course and all over the country.
Browse our notes for titles which look like what you need, you can preview any of the notes via a sample of the contents. After you're happy these are the notes you're after simply pop them into your shopping cart.
Document Preview
Extracts from the notes are below, to see the PDF you'll receive please use the links above
Reaction cooridnate
A reaction coordinate is an abstract coordinate used to measure the
progress of a chemical reaction
...
To measure this
progress, a reaction coordinate is chosen from a measurable coordinate
such as bond length, bond angle, a combination of bond length and
bond angle, or bond order
...
This profile will show the initial energy of the
reactants, the activation energy of the reaction, and the final energy of
the products
...
2013
General mechanisms of catalysis:
General acid-base catalysis
Catalysis by approximation
Covalent catalysis
Electrostatic catalysis
Metal ion catalysis
Mechanisms of catalysis
Proximity and orientation effects
•
Proximity: Reaction between bound molecules doesn't require an
improbable collision of 2 molecules -- they're already in "contact"
(increases the local concentration of reactants)
•
Orientation: Reactants are not only near each other on enzyme,
they're oriented in optimal position to react, so the improbability of
colliding in correct orientation is taken care of
Mechanisms of catalysis
Electrostatic catalysis
•
When substrate binds to enzyme, water is usually excluded from
active site (desolvation)
– causes local dielectric constant to be lower, which enhances
electrostatic interactions in the active site, and also
– results in protection of reactive groups from water, so water doesn't
react to form unwanted biproducts
...
g
...
Enzyme avoids unstable charged intermediates in reaction (which
would have high free energies) by:
– donating a proton (act as a general acid), or
– accepting a proton (abstract a proton, act as a general base)
•
•
If a group donates a proton (acts as a general acid) in chemical
mechanism, it has to get a proton (a different one!) back (act as a
general base) by end of catalytic cycle, and vice versa
Protein functional groups that can function as general acid/base
catalysts:
– e
...
His imidazole, α-amino group, α-carboxyl group, thiol of Cys, R
group carboxyls of Glu, Asp, aromatic OH of Tyr, etc
Mechanisms of catalysis
Mechanisms of catalysis
Acid-base catalysis
– E
...
Acids facilitate the removal of leaving groups:
R3C
O
R’
O
R’ + H
R3CX + -OR’
XR3C
+
R3C
+
O
X-
H
R’
R3CX + HOR’
Mechanisms of catalysis
Covalent catalysis
• Rate enhancement by the transient formation of a catalystsubstrate covalent bond
– Serine proteases: acyl-serine intermediate
– Cysteine proteases: acyl-cystein intermediate
– Protein kinases and phosphatases: phospho-amino acid intermediates
– Pyridoxal-cont’g enzymes: (lysine-NH2) Schiff bases
• Nucleophilic catalysis: donation of electrons from enzyme
nucleophile to a substrate
– side chains of His, Cys, Asp, Lys and Ser can participate in covalent
catalysis by acting as nucleophiles
• Electrophilic catalysis: covalent intermediate btw the cationic
electrophile of the enzyme and an electron rich portion of the
substrate molecule
– The a
...
g
...
g
...
g
...
7 down to 7
...
• Water then
displaces the
product, starting
the cycle again
...
A third
Zn ligand is either a glutamic acid (thermolysin, neprilysin,
alanyl aminopeptidase) or a histidine (astacin, serralysin)
...
The
catalytic mechanism involves formation of a non covalent
tetrahedral intermediate after the attack of a zinc-bound water
molecule on the carbonyl group of the scissile bond
...
EXAMPLES:
Matrix metalloproteinases (MMPs) are a family of enzymes that are responsible for the
degradation of extracellular matrix components such as collagen, laminin and
proteoglycans
...
ACE is a metalloprotease that catalyses the conversion of angiotensin I into angiotensin
II, which leads to vasoconstriction
...
Peptidoglycan and Lysozyme
• Peptidoglycan is a
polysaccharide found in
many bacterial cell walls
• Cleavage of the cell wall
leads to the lysis of
bacteria
• Lysozyme is an
antibacterial enzyme
General Acid-Base + Covalent Catalysis:
Cleavage of Peptidoglycan by Lysozyme
X-ray structures of
lysozyme with bound
substrate analogs show
that the C-1 carbon is
located between Glu 35
and Asp 52 residues
...
Quantitative studies showed that observed
• rate enhancement cannot only be explained with above mechanisms and
• we know that enzymes are conformationally dynamic
1
...
Some enzymes operate with kinetics which are faster than what would be predicted by
the classical ΔG‡
...
Quantum tunneling for protons has been observed in tryptamine oxidation by
aromatic amine dehydrogenase and a classic example is yeast alcohol dehydrogenase
...
However, the tunneling contribution (typically enhancing rate constants by a factor of
~1000 compared to the rate of reaction for the classical 'over the barrier' route) is likely
crucial to the viability of biological organisms
...
In 1971-1972 the first quantum-mechanical model of enzyme catalysis was formulated
...
The metal binds to
the charged intermediate
This charge stabilization of the TS is often called electrostatic
catalysis
This method is likely to be found in many enzymes since nearly 1/3
of all enzymes require metal ions
Examples of metal ion catalysis
Another classic
example of an
enzyme using metal
ion catalysis is
carboxypeptidase A
(an exopeptidase)
using Zn2+ in catalysis
(preference for a