CHM3930 Lecture Notes - Lecture 2: Drug Discovery, X-Ray Crystallography, Cyclic Adenosine Monophosphate
20 Jun 2018
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Week 2 -Drug targets: Enzymes, Receptors and Lipids
SDL + Lecture part 2: Enzymes
Enzymes: The catalysis of proteins
oCatalysts– provide a reaction surface
oActive site -often more hydrophobic than rest of enzyme
oSubstrate binding -positioned to enable “transition state” complex to be achieved
Lock and key or
Induced fit
oAspects of enzyme catalysts to consider:
Binding mechanisms
Acid-base catalysts
Nucleophilic groups
Cofactors
Nomenclature of enzymes
Characteristics:
oCatalytic power -rate up to ~ 1016 vs uncatalysed
oSpecificity -substrates are specific, so no side reactions occur…enzymes are selective
oRegulation - important to control these reactions (more later….)
Enzymes lower the EA of a reaction through the formation of a new transition state
Thermodynamically, the energy is related to the rate and equilibrium constants
DG = - RT ln(K)
And the rate constant
k = Ae-E/RT
find more resources at oneclass.com
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Thermodynamically, all that needs to be done is lower the free energy for the reactants to
undergo reaction
oDecrease enthalpy/make enthalpy more negative (ΔH)
oIncrease entropy/make more positive (ΔS)
oWhich all decreases Gibbs Free energy (ΔG = ΔH - TΔS)
1. Enzyme acts to weaken the C=O bond, thus helps in reaching transition state quicker
2. Enzyme makes ΔS more positive, by making the substrate more ordered in ES complex
Important Enzymic reactions:
pKa (Histidine) =7/8 neutral
can act as weak base (in a local pocket in the absence of water)
Stabilised by resonance structures
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Week 2 -drug targets: enzymes, receptors and lipids. Enzymes: the catalysis of proteins: catalysts provide a reaction surface, active site -often more hydrophobic than rest of enzyme, substrate binding -positioned to enable transition state complex to be achieved. Induced fit: aspects of enzyme catalysts to consider: Characteristics: catalytic power -rate up to ~ 1016 vs uncatalysed, specificity -substrates are specific, so no side reactions occur enzymes are selective, regulation - important to control these reactions (more later . ) Enzymes lower the ea of a reaction through the formation of a new transition state. Thermodynamically, the energy is related to the rate and equilibrium constants. Dg = - rt ln(k) k = ae-e/rt. Important enzymic reactions: pka (histidine) =7/8 neutral can act as weak base (in a local pocket in the absence of water) These three make up a catalytic triad: make serine a more affective nucleophile, change peptide bond to ester bond, water can hydrolyse ester bond better.
