Question

In hemoglobin, the innate affinity of Heme for carbon monoxide is diminished by the presence of

• A. His F-8
• B. His E-7
• C. Gly B-6
• D. Thr C-4

Hint:

The distal histidine (His E7) sterically hinders the linear binding geometry that carbon monoxide prefers.

Answer 1

The Correct Option is B

Step 1: Recall the globin fold and its key histidines.
Each globin chain of hemoglobin folds around a heme group, and two histidine residues sit close to the iron atom of heme. The proximal histidine, called His F8, sits directly below the iron and anchors it to the globin chain through a direct bond. The distal histidine, called His E7, sits on the opposite side of the heme, facing the pocket where oxygen or carbon monoxide binds, but it does not bond directly to the iron.

Step 2: Understand why free heme binds carbon monoxide so strongly.
Free heme, outside a protein, binds carbon monoxide about 25,000 times more strongly than it binds oxygen, because carbon monoxide can approach the iron in a straight, linear geometry that fits perfectly.

Step 3: Understand the role of His E7 inside hemoglobin.
Inside the globin pocket, the distal histidine (His E7) sits right where a straight-on approach of carbon monoxide would need to go. Its bulky side chain forces the carbon monoxide molecule to bind at a tilted, less favourable angle instead of a perfectly straight one, and it can also form a weak hydrogen bond that favours the bent binding of oxygen over the straight binding preferred by carbon monoxide. This steric hindrance cuts the affinity of heme for carbon monoxide down from 25,000-fold to only about 200-fold greater than oxygen.

Step 4: Rule out the other residues.
His F8 (the proximal histidine) holds the iron in place and is essential for oxygen binding overall, but it does not specifically block the linear approach of carbon monoxide, since it sits on the opposite face of the heme. Gly B6 and Thr C4 are structural residues involved in maintaining the shape of the heme pocket and chain packing; they are not the specific residues responsible for hindering carbon monoxide's straight-on binding geometry.

Step 5: Final Answer:
The distal histidine, His E7, is the residue that diminishes heme's innate affinity for carbon monoxide, option (2).