Structural insight into the interaction of O-acetylserine sulfhydrylase with competitive, peptidic inhibitors by saturation transfer difference-NMR
Structural insight into the interaction of O-acetylserine sulfhydrylase with competitive, peptidic inhibitors by saturation transfer difference-NMR
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DOI：
10.1002/1873-3468.12126
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发表时间：
2016-04-01
期刊：
影响因子：
3.5
通讯作者：
Mozzarelli, Andrea
中科院分区：
文献类型：
--
作者：
Benoni, Roberto;Pertinhez, Thelma A.;Mozzarelli, Andrea
O-乙酰丝氨酸硫化氢解酶（OASS）是细菌中半胱氨酸生物合成最后一步的催化酶，参与抗生素耐药性和生物膜形成。由于哺乳动物缺乏 OASS，因此它是抗菌药物的潜在目标。然而，已经开发出有限数量的抑制剂并与 OASS 复合结晶。 STD-NMR 用于研究抑制性五肽 MNYDI 与鼠伤寒沙门氏菌的 CysK 和 CysM OASS 同工酶的相互作用。结果与对接和 SAR 研究非常一致，并证实了 C 末端 Ile5 和 P3 上的芳基部分在决定亲和力中发挥的重要作用。
O-acetylserine sulfhydrylase (OASS), the enzyme catalysing the last step of cysteine biosynthesis in bacteria, is involved in antibiotic resistance and biofilm formation. Since mammals lack OASS, it is a potential target for antimicrobials. However, a limited number of inhibitors has been developed and crystallized in complex with OASS. STD-NMR was applied to study the interaction of the inhibitory pentapeptide MNYDI with the CysK and CysM OASS isozymes from Salmonella Typhimurium. Results are in excellent agreement with docking and SAR studies and confirm the important role played by the C-terminal Ile5 and the arylic moiety at P3 in dictating affinity.