Identification of potential inhibitors against Staphylococcus aureus shikimate dehydrogenase through virtual screening and susceptibility test.

IF 5.6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-01-17 DOI:10.1080/14756366.2024.2301768

Mengfan Zhu, Jinfeng Qu, Qi Deng

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Abstract

Staphylococcus aureus shikimate dehydrogenase (SaSDH) plays a crucial role in the growth of Staphylococcus aureus (S. aureus), but absent in mammals and therefore a potential target for antibacterial drugs to treat drug-resistant S. aureus infection. In this study, a 3D model of SaSDH was constructed by homology modelling and inhibitors of SaSDH were screened through virtual screening. (-)-Gallocatechin gallate and rhodiosin were identified as inhibitors with K_is of 2.47 μM and 73.38 μM, respectively. Molecular docking and isothermal titration calorimetry showed that both inhibitors interact with SaSDH with a K_D of 44.65 μM for (-)-gallocatechin gallate and 16.45 μM for rhodiosin. Both inhibitors had antibacterial activity, showing MICs of 50 μg/mL for (-)-gallocatechin gallate and 250 μg/mL for rhodiosin against S. aureus. The current findings have the potential for identification of drugs to treat S. aureus infections by targeting SaSDH.

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通过虚拟筛选和药敏试验鉴定金黄色葡萄球菌莽草酸脱氢酶的潜在抑制剂。

金黄色葡萄球菌莽草酸脱氢酶（SaSDH）对金黄色葡萄球菌（S. aureus）的生长起着至关重要的作用，但在哺乳动物中却不存在，因此是治疗耐药金黄色葡萄球菌感染的抗菌药物的潜在靶点。本研究通过同源建模构建了 SaSDH 的三维模型，并通过虚拟筛选筛选出了 SaSDH 的抑制剂。(-)-没食子儿茶素没食子酸酯和红景天素被确定为抑制剂，其 Kis 分别为 2.47 μM 和 73.38 μM。分子对接和等温滴定量热法表明，这两种抑制剂都能与 SaSDH 发生作用，(-)-没食子儿茶素没食子酸酯的 KD 为 44.65 μM，红景天素的 KD 为 16.45 μM。两种抑制剂都具有抗菌活性，其中(-)-没食子儿茶素没食子酸酯对金黄色葡萄球菌的抑菌浓度为 50 μg/mL，红豆杉素为 250 μg/mL。目前的研究结果有望鉴定出通过靶向 SaSDH 治疗金黄色葡萄球菌感染的药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Enzyme Inhibition and Medicinal Chemistry 医学-生化与分子生物学

CiteScore

10.30

自引率

10.70%

发文量

195

审稿时长

4-8 weeks

期刊介绍： Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.