bibc 102 announcements
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BIBC 102 ANNOUNCEMENTS. Randy ’ s bipartite office hours Tue 2 :30 -3:30 pm Wed 2:30-3:30 pm 2130 Pacific Hall. BIBC 102 Web Site. http://courses.ucsd.edu/rhampton/bibc102/. Soft Reserves lecture slides are available. Near Hi Thai. . BIBC 102 ANNOUNCEMENTS. BIBC 102 ANNOUNCEMENTS. - PowerPoint PPT PresentationTRANSCRIPT
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Lecture 2 Slides
BIBC 102 ANNOUNCEMENTS
http://courses.ucsd.edu/rhampton/bibc102/
Randy’s bipartite office hoursMon 2-3 pmTue 2-3 pm 2130 Pacific Hall
BIBC 102 Web Site
Soft Reserves lecture slides are available. Near Hi Thai.
BIBC 102 ANNOUNCEMENTS
BIBC 102 ANNOUNCEMENTS
Principles of Biochemistry,6th edLehninger, Nelson and Cox
Will be on reserve at the Biomedical Library, but not Geisel Library
Activation energy and reaction rate
fig 6-2
Activation energy and reaction rate
fig 6-3
What is the relation between changes in activation energy
and reaction rate?
Activation energy and reaction rate
S Pk dS/dt = k[S]
blue terms areconstant whentemperature isconstant...
Activation energy and reaction rate
designate blue terms as constants
Activation energy and reaction rate
call DG‡ = A for simplicity
Lowering activation energy …
Lowering activation energy …
when DG‡ is lowered by this amount: d
the rate constant is increased by this factor:
note the following features:lowering DG‡ makes reaction faster
identical effect on both directions
how big a deal is this?
recall that C2 = RT
at body temp, RT= 2573 J/mole
so if DG‡ changes by the value of onehydrogen bond (~20 kJ/mole)
rate enhancement is e7.8 = 2440
If you have not alreadyplease read
LIGAND BINDINGand
ENZYME CATALYSIS
Ligand Binding
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Does this form make intuitive sense?
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when there is no L, LB is also 0
as L gets big, LB approaches B saturable
Binding isotherm
rh rectangular hyperbola
Enzyme kinetics: binding and beyond
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when there is no S, reaction rate is 0
as S gets big, rate reaches a maximumsaturable
Michaelis-Menten Equation
Vo = Vmax S Km + S
again, a rectangular hyperbola MaudMenten
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Michaelis-Menten Equation
Vo = Vmax S Km + S
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when there is no S, V0 is also 0
as S gets big, V0 approaches Vmax
saturable
fig 6-11
how fast can an enzyme “do” a reaction?
table 6-7
Vmax = kcat[E]T
Competition for binding
rhfeature of saturability
remember to tellthem about I and Y
fig 6-15
action of a competitive enzyme inhibitor
fig 6-15
action of a uncompetitive inhibitor
fig 6-16catalytic action of enzyme causes
permanent covalent inhibition
a “suicide” inhibitor
fig 6-18
CHYMOTRYPSIN: a protease
fig 6-21
catalytictriad
fig 6-21
fig 6-21
fig 6-21
fig 6-21
fig 6-21
fig 6-21
fig 6-21
fig 6-21
Why do we need these details? an example:
The HIV Protease: cleaves single HIV-encodedpolypeptide into various proteins needed forviral replicationSpecific inhibitors of the HIV protease weredeveloped by an intimate understanding of thestructure and mechanism of the enzyme
amprenavir
Agenerase®
Now many HIV protease inhibitors
fig 6-30
amprenavir in HIV protease active site
hexokinase reaction
pg 212
fig 6-22
hexokinase
fig 6-22
hexokinase
induced fit
fig 6-22
site of Pi transfer
ATP
glucose transfer of Pfrom ATP
ATP
xyulose hydrolysis of ATP
C6
Regulation by phosphorylation: general case
fig 6-35
Regulation by phosphorylation: general case
switchable changes in activitycan activate or diminish activity
fig 6-36 ish
phosphorylation of glycogen phosphorylase
phosphorylatedenzyme more active
dephosphorylatedenzyme less active
Many covalent modifications
Many covalent modifications
COOPERATIVITYand
ALLOSTERICREGULATION
Simple binding:
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one K describes whole curve
Cooperative binding: hemoglobin vs. myoglobin
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K is NOT constant
Cooperative binding
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sigmoidal (“s-ish”) curve shape
“K” is a function of ligand concentration
protein has multiple subunits (4o structure)*
myoglobin hemoglobin*empiricalobservation
S P
enzyme with tertiary structure: single subunit
enzyme with quaternary structure: multiple subunits
this sort of structure allowsthe concentration of S toalter the the action of theenzyme on S...
XXX
S
P
single subunit shows M&M kinetics
multiple subunits allows sigmoidal kinetics
Vo
S
Vo cooperativity
S
when S is highE gets busy!!
Cooperative enzyme
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sigmoidal (“s-ish”) curve shape
“Km” is a function of substrate concentration
protein has multiple subunits (4o structure)
allows regulation by substrate orby unrelated molecules
not a constant!!
fig 6-34
Cooperative enzyme: sigmoidal rate curve
no constantKm for this
curve!!
Effect of cooperativity: from sluggish to steep
(table 15-2)
this sort of structure allowsthe concentration of S toalter the the action of theenzyme on S...
this sort of structure allows the concentration of R to alter the the action of the enzyme on S...
S
PS
R
S
fig 6-31
fig 6-34
Allosteric regulators
activator
inhibitor
rhJacques Monod
Le deuxième secret de la vie !!
Allosteric regulation
fig 6-32
Aspartate transcarbamoylase
catalytic
regulatory
fig 6-32
branch point in aromatic aametabolism...
chorismate mutase: a simple allosteric enzyme
chorismate mutase: branch point in aa metabolism
tryptophan tyrosine
chorismate mutase
no regulator
[chorismate]
plustyrosine
plustryptophan
Vo
chorismate mutase: branch point in aa metabolism
tryptophanactivates CM
tyrosineinhibits CM
CM
chorismate mutase: a homodimer
active site
regulatorbinding
4o structure is required for allostery!
chorismate mutase
small spatial differences instructure underlie regulation
small spatial differences instructure underlie regulation
chorismate mutase