Why 2,3-bisphosphoglycerate (BPG) does not bind oxyhemoglobin effectively Identify the structural reason R-state hemoglobin excludes BPG from its central cavity.

Introduction / Context:
BPG is a key heterotropic effector that stabilizes the T state of adult hemoglobin by binding in the central cavity between beta subunits. Understanding why oxyhemoglobin has low BPG affinity explains rightward shifts of the O2 dissociation curve under physiological conditions.

Given Data / Assumptions:

• T state has a larger central cavity lined with positively charged residues that coordinate BPG.
• R state has a narrower central cavity.

Concept / Approach:
Upon oxygenation, hemoglobin undergoes quaternary rearrangement to the R state, shrinking the central cavity. The reduced cavity size and altered residue geometry preclude effective BPG binding, thereby further stabilizing the high-affinity conformation.

Step-by-Step Solution:
Recall BPG binds in the central cavity of deoxyhemoglobin (T state).O2 binding promotes T → R transition that narrows the cavity.Conclude that the pocket is too small for BPG in the R state.

Verification / Alternative check:
Structural comparisons of deoxy versus oxy hemoglobin show the cavity collapse upon oxygenation, correlating with loss of BPG density in crystallography.

Why Other Options Are Wrong:
BPG does not bind the heme; proximal His movement is not the direct cause of BPG displacement; equal affinity in T and R contradicts the known effect; chemical degradation of BPG is not part of the mechanism.

Common Pitfalls:
Assuming BPG competes at the heme site; it binds allosterically in the central cavity.

Final Answer:
Its binding pocket becomes too small to accommodate BPG.