Question

Question: Dicyclohexylcarbodiimide (DCCD) is a reagent that reacts with Asp

or Glu residues.

Explain why the reaction of DCCD with the c subunits of F₁F₀-ATPase

blocks its ATP-synthesizing activity.

Short answer

DCCD binds to the carboxy terminal of the H⁺ binding Asp61 residue c, inhibiting the F₀F₁ coupling reaction.

Step-by-step solution

Step1: Dicyclohexylcarbodiimide

Dicyclohexylcarbodiimide (DCCD) is a -ATP synthase inhibitor that binds covalently to the carboxylic end of the c subunit. A c subunit is a proton translocating subunit with two alpha transmembrane helices connected by a short polar loop. Protons bind to Asp61 of each c subunit, and this protonation and deprotonation of the residue changes the subunit's conformation.

Blockage of ATP-synthesizing activity

The substitution of Asp61 for other residues inhibits proton translocation and thus ATP hydrolysis by ATP synthase. DCCD reacts with the binding carboxy terminal of the Asp61 residue c subunit, preventing the coupling reaction of F₀F₁.