In hemoglobin, two specific histidine residues play critical roles in heme function. The proximal histidine (F8) directly coordinates the iron atom. What is the function of the distal histidine (E7)?

• A It directly coordinates the heme iron atom
• B It stabilizes bound oxygen through hydrogen bonding and sterically hinders carbon monoxide binding ✓
• C It forms the intersubunit salt bridges that stabilize the T-state
• D It binds 2,3-BPG in the central cavity of the tetramer

Explanation

The distal histidine (E7) does not coordinate iron but sits on the oxygen-binding side. It hydrogen-bonds to bound O2, stabilizing it, and sterically hinders CO binding (reducing CO's affinity advantage from 25,000 to about 200-fold). The proximal histidine (F8) is the one that directly coordinates the heme iron. Salt bridges involve other residues.

Reference: Harper's Biochemistry, 31st ed.

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