How the beta part of the voltage-controlled potassium channel works and selects molecules

Recombinant rat Kvbeta2 catalyzes the reduction of a wide range of aldehydes and ketones at a rate of 0.06-0.2 min(-1).

• Kvbeta2 shows a hyperbolic dependence on substrate concentration without evidence of allosteric cooperativity.
• Substituting Tyr-90 with phenylalanine prevents catalysis, confirming its role as a crucial catalytic residue.
• The enzyme effectively reduces various carbonyl compounds, including aromatic carbonyls and electrophilic aldehydes.
• Initial velocity profiles suggest an ordered bi-bi rapid equilibrium mechanism with NADPH binding occurring before carbonyl binding.
• Significant primary kinetic isotope effects of 2.0-3.1 indicate that the bond-breaking step is rate-limiting during the reaction.
• Structure-activity relationships reveal that electronic interactions dominate substrate binding, with minimal charge development during the transition state.

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