bibc 102 announcements
DESCRIPTION
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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rh
Lecture 2 Slides
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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.
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BIBC 102 ANNOUNCEMENTS
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BIBC 102 ANNOUNCEMENTS
Principles of Biochemistry,6th edLehninger, Nelson and Cox
Will be on reserve at the Biomedical Library, but not Geisel Library
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Activation energy and reaction rate
fig 6-2
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Activation energy and reaction rate
fig 6-3
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What is the relation between changes in activation energy
and reaction rate?
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Activation energy and reaction rate
S Pk dS/dt = k[S]
blue terms areconstant whentemperature isconstant...
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Activation energy and reaction rate
designate blue terms as constants
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Activation energy and reaction rate
call DG‡ = A for simplicity
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Lowering activation energy …
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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
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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
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If you have not alreadyplease read
LIGAND BINDINGand
ENZYME CATALYSIS
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Ligand Binding
rh
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Does this form make intuitive sense?
rh
when there is no L, LB is also 0
as L gets big, LB approaches B saturable
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Binding isotherm
rh rectangular hyperbola
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Enzyme kinetics: binding and beyond
rh
when there is no S, reaction rate is 0
as S gets big, rate reaches a maximumsaturable
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Michaelis-Menten Equation
Vo = Vmax S Km + S
again, a rectangular hyperbola MaudMenten
rh
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Michaelis-Menten Equation
Vo = Vmax S Km + S
rh
when there is no S, V0 is also 0
as S gets big, V0 approaches Vmax
saturable
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fig 6-11
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how fast can an enzyme “do” a reaction?
table 6-7
Vmax = kcat[E]T
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Competition for binding
rhfeature of saturability
remember to tellthem about I and Y
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fig 6-15
action of a competitive enzyme inhibitor
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fig 6-15
action of a uncompetitive inhibitor
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fig 6-16catalytic action of enzyme causes
permanent covalent inhibition
a “suicide” inhibitor
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fig 6-18
CHYMOTRYPSIN: a protease
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fig 6-21
catalytictriad
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fig 6-21
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fig 6-21
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fig 6-21
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fig 6-21
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fig 6-21
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fig 6-21
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fig 6-21
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fig 6-21
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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®
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Now many HIV protease inhibitors
fig 6-30
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amprenavir in HIV protease active site
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hexokinase reaction
pg 212
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fig 6-22
hexokinase
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fig 6-22
hexokinase
induced fit
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fig 6-22
site of Pi transfer
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ATP
glucose transfer of Pfrom ATP
ATP
xyulose hydrolysis of ATP
C6
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Regulation by phosphorylation: general case
fig 6-35
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Regulation by phosphorylation: general case
switchable changes in activitycan activate or diminish activity
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fig 6-36 ish
phosphorylation of glycogen phosphorylase
phosphorylatedenzyme more active
dephosphorylatedenzyme less active
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Many covalent modifications
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Many covalent modifications
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COOPERATIVITYand
ALLOSTERICREGULATION
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Simple binding:
rh
one K describes whole curve
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Cooperative binding: hemoglobin vs. myoglobin
rh
K is NOT constant
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Cooperative binding
rh
sigmoidal (“s-ish”) curve shape
“K” is a function of ligand concentration
protein has multiple subunits (4o structure)*
myoglobin hemoglobin*empiricalobservation
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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
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S
P
single subunit shows M&M kinetics
multiple subunits allows sigmoidal kinetics
Vo
S
Vo cooperativity
S
when S is highE gets busy!!
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Cooperative enzyme
rh
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!!
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fig 6-34
Cooperative enzyme: sigmoidal rate curve
no constantKm for this
curve!!
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Effect of cooperativity: from sluggish to steep
(table 15-2)
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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
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fig 6-31
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fig 6-34
Allosteric regulators
activator
inhibitor
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rhJacques Monod
Le deuxième secret de la vie !!
Allosteric regulation
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fig 6-32
Aspartate transcarbamoylase
catalytic
regulatory
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fig 6-32
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branch point in aromatic aametabolism...
chorismate mutase: a simple allosteric enzyme
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chorismate mutase: branch point in aa metabolism
tryptophan tyrosine
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chorismate mutase
no regulator
[chorismate]
plustyrosine
plustryptophan
Vo
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chorismate mutase: branch point in aa metabolism
tryptophanactivates CM
tyrosineinhibits CM
CM
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chorismate mutase: a homodimer
active site
regulatorbinding
4o structure is required for allostery!
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chorismate mutase
small spatial differences instructure underlie regulation
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small spatial differences instructure underlie regulation
chorismate mutase