Jung M J, Metcalf B W, Lippert B, Casara P
Biochemistry. 1978 Jun 27;17(13):2628-32. doi: 10.1021/bi00606a026.
4-Aminohex-5-ynoic acid inhibits bacterial glutamic acid decarboxylase in a time-dependent irreversible manner. The inhibition is stereospecific and requires the abstraction of the propargylic hydrogen from 4(R)-(--)-4-aminohex-5-ynoic acid. This leads to the generation of a reactive alkylating agent in the active site which can react with a nucleophilic residue. At complete inhibition, there is incorporation of one molecule of inhibitor per pyridoxal binding site. If the decarboxylation of glutamate occurs with retention of configuration, the irreversible inhibition of this enzyme by the 4-(R) isomer can be rationalized on the basis of reversibility of the protonation step in the normal catalytic mechanism.
4-氨基己-5-炔酸以时间依赖性不可逆方式抑制细菌谷氨酸脱羧酶。这种抑制具有立体特异性，需要从4(R)-(-)-4-氨基己-5-炔酸中提取炔丙基氢。这会在活性位点产生一种反应性烷基化剂，它可以与亲核残基反应。在完全抑制时，每个吡哆醛结合位点会掺入一分子抑制剂。如果谷氨酸脱羧反应发生时构型保持不变，那么4-(R)异构体对该酶的不可逆抑制可以基于正常催化机制中质子化步骤的可逆性来解释。
