enzyme-substrate complex

Meaning: The enzyme-substrate complex (ES) forms when a substrate binds the active site, usually through weak noncovalent interactions such as hydrogen bonds, ionic attractions and hydrophobic contacts. Two models describe the binding: lock-and-key (a rigid, complementary site) and induced fit (the site reshapes around the substrate), with induced fit generally favored. In the complex the enzyme stabilizes the transition state, lowering activation energy and raising the rate without changing ΔG or Keq.

Equation: E + S ⇌ ES → E + P, where E is free enzyme, S is substrate, ES is the complex and P is product (all in mol/L). v = kcat[ES] and Vmax = kcat[E]total, where v is the rate (M/s) and kcat is the turnover number (s⁻¹).

On the MCAT: In Michaelis-Menten graphs, the rate climbs with [S] until nearly all enzyme is in ES form, giving Vmax. A competitive inhibitor binds free enzyme instead of forming ES, so Vmax is unchanged and apparent Km rises. An uncompetitive inhibitor binds only ES and lowers both Vmax and apparent Km.

Common confusion: ES is not the transition state. ES sits in an energy well, while the transition state is the energy peak between ES and the enzyme-product complex. The enzyme is also not used up; it is released unchanged.