Exam #1 Flashcards
Isoelectric Point Calculation
Average the pKas= pKa1+pKa2/2
Spontaneous
Delta G < 0, reaction will move to the right
Enthalpy
Delta H, Delta H < 0= exothermic and favorable
heat released - Delta H when chemical bonds form
heat absorbed + Delta H when chemical bonds break
Non-Spontaneous
Delta G > 0, reaction will move to the left
Entropy
Delta S, Disorder of System,
Delta S > 0= favorable
Thermodynamics
study of energy, transformation of energy from one form to another
Covalent Bonds
atoms share at least 2 electrons
Ionic Bonds
no sharing, steals electrons, attractive force from opposite charges
Dipole-Dipole Interactions
same as ionic, with something with no definitive charge
Hydrogen Bonds
special, don’t bond to H, bond 2 electronegative atoms (O or N) with it and one has a lone pair
Van der Waals
low energy, not significant, radius distance between center of atom and end, they come close but don’t invade personal space, when they get too close they repel
Hydrophilic
water likes to interact with hydrogen bonds
Hydrophobic
doesn’t like interacting with water, does Van der Waals
Amphipathic
hates to interact with both
Amphiphilic
likes to interact with both
Hydrophobic effect
water pushes hydrophobic molecules together
Acids
donates proton to water
HA (acid) + H2O (backward and forward arrows) A (CB) + H3O+
Base
accepts proton usually from a water
B + H2O (backward and forward arrow which establishes equilibria) BH (CA) + OH-
Equilibrium
-logKa= pKa (measure of how much a group wants a proton)
pH
measure of how many Hs are in the solution
Henderson-Hasselbach Equation
pH= pKa + log [base]/[acid]
KEY INFO ABOUT pH esp when COMBINING AMINO ACIDS
when pH is BELOW the pKa, the group is protonated
Proteins
bind things
Binding Pocket
area on proteins with binding properties
protein will have surface designed to interact with particular ligand
Ligand
what it binds to, molecule which protein specifically interacts with
Binding a ligand
conformational change of protein
catalyze a chemical reaction
inhibit or alter normal function of protein
do none of the above
Types of Interactions
Hydrogen Bonds, electrostatic, van der Waals ALL NON-COVALENT
“specific” may not be that specific
protein may have different ligands and ligand may interact with different proteins
Affinity
preference of a protein for a ligand is its AFFINITY for that ligand
High affinity
binds tightly
lots of interactions
small Kd
Low affinity
binds loosely
less interactions
large Kd
Transiently
proteins w/ ligands transiently–> protein: ligand interaction from equilibria
Fraction Disassociation Equation
Theta= [L]/Kd+[L]
Two-Log Rule of Affinity
protein-ligand binding is linearly related to [ligand] over a span of two logs relative to the Kd
below 0.1XKd there is minimal protein occupancy (drug will have no real effect b/c it won’t find its target)
above 10XKd saturation approaches (interactions w/ other proteins can lead to side-effects)
Myoglobin
oxygen-storer
single polypeptide chain
made up of 8 alpha helices NO BETA SHEETS
Heme prosthetic group–> co-factor, critical (covalently bonded to protein)
Binds O2 by means of Fe2+ contained in heme prosthetic group
Heme
Nitrogens are holding on to iron equally (heme is conjugated), Fe is what interacts w/ O2, and heme binding to O2 is facilitated by 2 different histidines proximal and distal
Distal Histidine
very strong H-bond with molecular oxygen, heme bonds w/ CO much better than O2 x20,000 stronger for free heme alpha CO
Myoglobin Binds O2
[L]–> pO2
Kd–> P50
Theta= pO2/P50+pO2
P50 of myoglobin for O2 is 0.26 kPa
Myoglobin saturated at most biological pO2s
pO2 lungs: 13.3 kPa
pO2 tissue: 4 kPa
Hemoglobin
transporting O2 throughout body
higher P50 than myoglobin
tetramer (quaternary structure): 2 pairs of hemoglobins alpha beta, each monomer similar in structure to myoglobin
2 alpha and beta subunits, dimers
T State
“tense” LOW AFFINITY FOR O2
R State
“relaxed” HIGH AFFINITY FOR O2
T–R
O2 binding induces a conformational change
O2 coordinating w/ heme causes a conformationmotifs from T to R
R state has higher affinity for O2
Shift propagated throughout protein so each monomer enters R state even if it hasn’t bound O2 yet
Cooperativity
ligand binding at one site affects ligand binding at another site
Positive cooperativity
initial binding increases affinity for other ligand nH>1
Non-competitive cooperativity
ligand binding is independent for all sites nH=1
Negative cooperativity
initial binding decreases affinity for other ligand nH<1
Allostery
when protein conformational changes affect protein function
Why Hemoglobin is an ideal O2 transporter
cooperativity of hemoglobin makes it effective at both binding and increasing O2, dependent on O2
myoglobin only releases O2, when pO2 is very low
other factors enhance O2, release by stabilizing hemoglobin’s T state (BPG and pH/CO2 Bohr Effect)
Concerted (MWC) Model
only conformational change alters affinity for ligand
if one subunit changes state, they ALL change state
Sequential (KNF) Model
ligand binding alters affinity of own subunit and adjacent subunits
nH
found by looking at the slope where it varies from 1
BPG
binds in central cavity of T-state hemoglobin, stabilizing it
interacts with three positively charged amino acids (two His and one Lys) on each beta subunit
fetal hemoglobin features y subunits instead of beta subunits. Lower affinity for BPG
Stabilizing T state reduces affinity for O2 when then leads to release when/where it is needed
Bohr Effect
hemoglobin’s binding affinity for O2 inversely related to [H+] and pCO2
low pH–> protonation–> forms salt bridges in T-state and can stabilize T-state–> reduce affinity for O2 –> leads to release when/where it is needed
CO2 combines w/ H2O to make H2CO3 reducing pH
CO2 reacts with N-terminal amine group to form a carbamate, forms salt bridge that stabilizes T-state
