Ricard J, Noat G
J Theor Biol. 1985 Dec 21;117(4):633-49. doi: 10.1016/s0022-5193(85)80244-7.
The principles of structural kinetics, as applied to dimeric enzymes, allow us to understand how the strength of subunit coupling controls both substrate-binding co-operativity, under equilibrium conditions, and kinetic co-operativity, under steady state conditions. When subunits are loosely coupled, positive substrate-binding co-operativity may result in either an inhibition by excess substrate or a positive kinetic co-operativity. Alternatively, negative substrate-binding co-operativity is of necessity accompanied by negative kinetic co-operativity. Whereas the extent of negative kinetic co-operativity is attenuated with respect to the corresponding substrate-binding co-operativity, the positive kinetic co-operativity is amplified with respect to that of the substrate-binding co-operativity. Strong kinetic co-operativity cannot be generated by a loose coupling of subunits. If subunit is propagated to the other, the dimeric enzyme may display apparently surprising co-operativity effects. If the strain of the active sites generated by subunit coupling is relieved in the non-liganded and fully-liganded states, both substrate-binding co-operativity and kinetic co-operativity cannot be negative. If the strain of the active sites however, is not relieved in these states, negative substrate-binding co-operativity is accompanied by either a positive or a negative co-operativity. The possible occurrence of a reversal of kinetic co-operativity, with respect to substrate-binding co-operativity, is the direct consequence of quaternary constraints in the dimeric enzyme. Moreover, tight coupling between subunits may generate a positive kinetic co-operativity which is not associated with any substrate-binding co-operativity. In other words a dimeric enzyme may well bind the substrate in a non co-operative fashion and display a positive kinetic co-operativity generated by the strain of the active sites.
应用于二聚体酶的结构动力学原理，使我们能够理解亚基偶联强度如何在平衡条件下控制底物结合协同性，以及在稳态条件下控制动力学协同性。当亚基松散偶联时，正的底物结合协同性可能导致过量底物的抑制作用或正的动力学协同性。或者，负的底物结合协同性必然伴随着负的动力学协同性。虽然负的动力学协同性程度相对于相应的底物结合协同性有所减弱，但正的动力学协同性相对于底物结合协同性则被放大。亚基的松散偶联无法产生强的动力学协同性。如果亚基间的影响传递到另一个亚基，二聚体酶可能会表现出明显惊人的协同效应。如果亚基偶联产生的活性位点应变在非配体状态和完全配体状态下得到缓解，那么底物结合协同性和动力学协同性都不可能是负的。然而，如果活性位点的应变在这些状态下没有得到缓解，负的底物结合协同性会伴随着正的或负的协同性。动力学协同性相对于底物结合协同性可能发生逆转，这是二聚体酶四级结构限制的直接结果。此外，亚基之间的紧密偶联可能产生一种与任何底物结合协同性无关的正的动力学协同性。换句话说，二聚体酶很可能以非协同方式结合底物，并表现出由活性位点应变产生的正的动力学协同性。
