Can someone explain to me how 2,3 BPG works for hemoglobin?

BPG affects oxygen binding affinity by binding in a small cavity at the center axis of deoxygenated hemoglobin. In oxygenated hemoglobin, this cavity is too small to effectively accommodate 2,3-BPG. When bound, 2,3-BPG stabilizes the deoxygenated conformation of hemoglobin, greatly diminishing the binding of oxygen and facilitating oxygen unloading to actively respiring tissues.

How can oxygen be unloaded if the cavity is too small for 2,3 BPG to enter in the first place?
Or is this possible only when the hemoglobin is not fully oxygenated?

The binding of 2,3-BPG to hemoglobin occurs predominantly in the deoxygenated state, not the oxygenated state. When hemoglobin binds oxygen, it undergoes a conformational change that narrows the central cavity, making it difficult for 2,3-BPG to bind. However, when oxygen is released from the hemoglobin molecule, it undergoes another conformational change that opens up the cavity, allowing 2,3-BPG to bind.

So, oxygen unloading occurs when the hemoglobin is in the deoxygenated state, and it is during this state that 2,3-BPG has the opportunity to bind and stabilize the deoxygenated conformation. When 2,3-BPG is bound, it decreases the oxygen affinity of hemoglobin, making it easier for oxygen to dissociate from the molecule and be released to the tissues.

When hemoglobin is fully oxygenated, there is minimal binding of 2,3-BPG due to the conformational changes that occur upon oxygen binding. Therefore, the effect of 2,3-BPG on oxygen unloading is predominantly seen when the hemoglobin is in the deoxygenated state.