NOTHING IS REAL! EXAM 1 REVIEW Flashcards
Antigens are recognized with high affinity by antibodies because
the sequences of three hypervariable loops are selected in an immune response to exquisitely complement the 3D shape of the antigen.
kcat is what type of parameter?
Kinetic rate constant independent of enzyme or substrate concentration
Change in Km
noncompetitive (mixed)
Change in Km and Vmax
uncompetitive
change Vmax
competitive
The assigned reading “Therapeutic monoclonal antibodies,” describes several types of engineered antibody molecules that have been developed for therapeutics. Which of the names below DOES refer to a type of therapeutic monoclonal antibody?
Fab, BiTE, scFv
Twelve domains compose an IgG molecule. Of these domains,
all have two or more cysteine residues.
Ig chains
4: 2 heavy 2 light
Ig fold (Domain)
-sandwich of 2 antiparallel B-sheets
-disulfide bond linkage
-hydrophobic residues
-connected to each other by loops = flexible
Substrate enzyme interactions
-hydrophobic to hydrophobic
-H bonding
-coloumbic
KI
-dissociation constant
-analogous to KD
-low=more affinity
Cheng-Prusoff
relationship btw Ki and IC50
The development of an allosteric drug is attractive because
it is possible to consider ACTIVATING an enzyme target in treating a disease.
Darunavir
interacts with polypeptide backbone and catalytic asp residues from each subunit of HIV protease
The basis for selectivity of certain NSAIDS, such as celecoxib, for COX-2 over COX-1 is
the spatial complementarity between the inhibitor and COX-1 is poor
HIV protease
-homodimer
-heme group
-aspartic
Aspirin vs everything else on COX
acetylates SERINE residue near active site to block access
Mech-based inhibitors
-2-thioxanthines on MPO
TX2 on MPO
covalently bonded to heme via thioether bond
NSAIDs
block prostaglandin
COX-2 vs COX-1
small Valine residue
steric hinderance
Allosteric inhibitor kinetics
typically mixed
Allosteric inhibition
increase Km
Cytochrome inhibitor
-increase bioavailability/plasma levels of drug
-drug more potent
CYP3A4
-monoxygenase
-membrane bound
-activity and dosing of drugs
cytochrome catalytic activity
-insertion of OH from O2
-metabolism of fatty acids
-produce vitamin A and D
-detoxification
G is positive
NEED energy
SLC transporters
-large family
-most bio substrates
-NO energy
electrochemical transporters
-SLC (uni,sym,antiport)
SLC2
-glucose by uniport
SGLT (SLC5)
Na+/glucose
-Na+ provides energy to move glucose across gradient
-SYMPORT
ATP hydrolysis
-P-type (Na/K+ ATPase)
-ABC
ABC
-energy
-lipids
-P-glycoprotein
P-glycoprotein
hydrolysis of ATP drives NBDs apart and converts TMDs back
The A-form DNA helix
often occurs in formation of DNA-RNA hybrid helix.
B-DNA
-longer
-skinnier
-smaller diameter
-C’2 endo
-bigger pitch and twist
B-form major groove
wider and shallower
-highly accessible
Intercalators
-mod DNA locally
-mutagens
-stretch base pairs apart
-TOTO
-small molecules in mostly minor grooves
positive supercoiling
-left
-overwound
-hard to unwind good for bad condititons
topologically strained DNA
greater activity for transcription etc
TOP 1
- cuts one strand
- controlled rotation
- re-ligate
-NO ENERGY
-REMOVES supercoiling
TOP 2
- Cuts both strands
- Moves other strand through opening in cut strand
- re-ligate
-LK change by 2
-gyrase (adds negative)
-NEEDS ENERGY
TOP inhibitors
-trap complex of enzyme + DNA
-inhibit re-ligation
-topotecan and irinotecan
Nucleosome
DNA wrapped around histone octamer
Energy required to deform DNA
from electrostatic interactions between DNA backbone and histone side chains
HTH
-2 helices w short turn
-second helix binds major groove
-first helix stabilizes
Zinc Fingers
-a-helix binds
-ALSO recognizes RNA
-4 cys or 2 cys+2his
-tandem
bZIP
-leucine every 7th a-helix
-dimers
-arg and lys basic region binds major groove
-phosphate baxkbone and H bonding
HLH
-2 a-helix connected by loop
-4helix dimer
-extension of one a-helix binds major groove
CREB domains
-DBD (bzip): binding
-Activation domain (Q1 and2): interact with TFs
-protein interaction domain (KID): histone acetyltransferases
TBP TATA binding protein
B-sheet
-MINOR GROOVE
-bends TATA box
-binding directs assembly of initiation complex
Steroid nuclear receptors
-bind steroid then bind to DNA to activate transcription
-DBD-hinge-LBD