Davidson V L, Jones L H
Department of Biochemistry, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Biochim Biophys Acta. 1995 Sep 27;1252(1):146-50. doi: 10.1016/0167-4838(95)00114-a.
Phenylhydrazine has previously been shown to be an irreversible inactivator of the tryptophan tryptophylquinone (TTQ) enzyme methylamine dehydrogenase [Davidson, V.L. and Jones, L.H. (1992) Biochim. Biophys. Acta 1121, 104-110]. Structure-reactivity correlations have been performed to elucidate the mechanism by which this inactivation occurs. The reactions of a series of p-substituted phenylhydrazines with methylamine dehydrogenase were examined. Correlation with electronic substituent effects was observed. A Hammett plot of the second order inactivation rate constants versus sigma p exhibited a positive slope. Plots of these rate constants against substituent constants which reflected either resonance or field/inductive parameters for each p-substituent indicated that the rate was primarily influenced by resonance electronic effects. A Brønsted plot of the inactivation rate constant against pKa of each substituted phenylhydrazine yielded a beta-value (slope) of 0.7. Based upon these results, a reaction mechanism is proposed for the inactivation of methylamine dehydrogenase by phenylhydrazines, and a structure is proposed for the putative transition state for the rate-limiting step in the overall processes of binding and adduct formation by phenylhydrazine. The relevance of these results to the process of imine formation between substrate amines and TTQ during the normal catalytic process is also discussed.
此前已证明苯肼是色氨酸色氨酰醌（TTQ）酶甲胺脱氢酶的不可逆失活剂[戴维森，V.L.和琼斯，L.H.（1992年）《生物化学与生物物理学报》1121卷，第104 - 110页]。已进行结构 - 反应活性相关性研究以阐明这种失活发生的机制。研究了一系列对取代苯肼与甲胺脱氢酶的反应。观察到与电子取代基效应的相关性。二级失活速率常数对σp的哈米特图呈现正斜率。这些速率常数与反映每个对取代基的共振或场/诱导参数的取代基常数的图表明，速率主要受共振电子效应影响。失活速率常数对每个取代苯肼的pKa的布朗斯特图得出β值（斜率）为0.7。基于这些结果，提出了苯肼使甲胺脱氢酶失活的反应机制，并提出了苯肼在结合和加合物形成的整个过程中限速步骤的假定过渡态结构。还讨论了这些结果与正常催化过程中底物胺与TTQ之间亚胺形成过程的相关性。
