a Food and Drug Department , University of Parma , Parma , Italy.
b Latvian Institute of Organic Synthesis , Riga , Latvia.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):1343-1351. doi: 10.1080/14756366.2018.1504040.
O-acetylserine sulfhydrylase (OASS) is the pyridoxal 5'-phosphate dependent enzyme that catalyses the formation of L-cysteine in bacteria and plants. Its inactivation is pursued as a strategy for the identification of novel antibiotics that, targeting dispensable proteins, holds a great promise for circumventing resistance development. In the present study, we have investigated the reactivity of Salmonella enterica serovar Typhimurium OASS-A and OASS-B isozymes with fluoroalanine derivatives. Monofluoroalanine reacts with OASS-A and OASS-B forming either a stable or a metastable α-aminoacrylate Schiff's base, respectively, as proved by spectral changes. This finding indicates that monofluoroalanine is a substrate analogue, as previously found for other beta-halogenalanine derivatives. Trifluoroalanine caused different and time-dependent absorbance and fluorescence spectral changes for the two isozymes and is associated with irreversible inhibition. The time course of enzyme inactivation was found to be characterised by a biphasic behaviour. Partially distinct inactivation mechanisms for OASS-A and OASS-B are proposed.
O-乙酰丝氨酸巯基酶（OASS）是一种依赖于吡哆醛 5'-磷酸的酶，能够在细菌和植物中催化 L-半胱氨酸的形成。抑制其活性被视为鉴定新型抗生素的一种策略，因为这些抗生素针对非必需蛋白，有望避免产生耐药性。本研究调查了沙门氏菌 OASS-A 和 OASS-B 同工酶与氟代丙氨酸衍生物的反应性。单氟代丙氨酸与 OASS-A 和 OASS-B 分别形成稳定或亚稳定的α-氨基丙烯酸 Schiff 碱，这一点通过光谱变化得到证实。这一发现表明，单氟代丙氨酸是一种类似物，就像以前发现的其他β-卤代丙氨酸衍生物一样。三氟代丙氨酸引起两种同工酶的吸光度和荧光光谱发生不同且随时间变化的变化，并与不可逆抑制有关。发现酶失活的时间过程具有双相特征。提出了 OASS-A 和 OASS-B 具有部分不同的失活机制。
