Hemoglobin 2 Flashcards
What is a conformational change
A shift in the orientation of secondary structure(S)
What effect does the hisE7 have
His E7 is located on a different alpha helix than hisF8,
It makes the O2 bound in a bent position
- weakening the Fe++ O2 bond
- Makes the reaction easier to reverse
What change occurs when O2 binds to heme - how is this effect reduced
Oxygenated heme is in the plane state, pulling his8 into the binding site
- reduced by keeping his8 away from the binding site
What can cause conformational changes
pH
allosteric regulators
genetic or physiological changes
When/ how does hemoglobin become cooperative
what does this change
Without inhibitors in the R-state
When allosteric inhibitors are in place- they stabilise the T-state
creates sigmoidal curve
What are alosteric inhibitors of hemoglobin
CO2, H+, BPG
How does BPG interact with hemoglobin
Binds between beta chains in t-state
held in pocket by salt bridges, 4 his 2 lys to the -ve phosphates of BPG
- Highly produced in the tissue
stabilises the T state
How does CO2 and H+ relate to
- increase protonation of hist residues stronger ionic interactions with BPG
- directly binds to the amino terminal stabilising T state
- produced as waste product in tissue lowers pH
- emphasises the sigmoidal curve
What deos being cooperative change about the way your V [s] curve looks
from hyperbolic -> sigmoidal
curve shows increasing velocity depending on number of bound O2 in other subunits
reaches saturation at 4 O2 (all heme)
What is fetal hemoglobin + functional differences
Fetal hemoglobin = 2 alpha 2 gamma subunits
gamma - creates strionger O2 bindnig affinity = left pulled curve
- importnant to prevent loss at placenta
Weaker BPG binding = 2 ser instead to 2 his in binding site = less likely to bind BPG = less likely to become t state and lose O2
What is sickle cell animea
mutation- E6V (glu -> val)
creates a hydrophobic pocket in the T state due to proximity which favors this state = worse O2 binding and conformational change
gets stuck in blood vessles
can help creates resistance to maleria
What is two forms of treatment for sickle cell hemoglobin
1: CRISPER - upregulate transcription factors of gamma subchain
- increases amount of functional hemoglobin
however is exspensive
2: Voxelotor: oxygen affninty modulator
- promote affinity to the R state
