Virology Unit, Immunovirology Laboratory, Institut Pasteur du Maroc, 20360 Casablanca, Morocco.
Laboratory of Biology and Health, URAC 34, Faculty of Sciences Ben M'Sik Hassan II University of Casablanca, Morocco.
Biomed Res Int. 2021 Oct 19;2021:9982729. doi: 10.1155/2021/9982729. eCollection 2021.
The human transmembrane protease serine 2 () protein plays an important role in prostate cancer progression. It also facilitates viral entry into target cells by proteolytically cleaving and activating the S protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the current study, we used different available tools like SIFT, PolyPhen2.0, PROVEAN, SNAP2, PMut, MutPred2, I-Mutant Suite, MUpro, iStable, ConSurf, ModPred, SwissModel, PROCHECK, Verify3D, and TM-align to identify the most deleterious variants and to explore possible effects on the stability, structure, and function. The six missense variants tested were evaluated to have deleterious effects on the protein by SIFT, PolyPhen2.0, PROVEAN, SNAP2, and PMut. Additionally, V160M, G181R, R240C, P335L, G432A, and D435Y variants showed a decrease in stability by at least 2 servers; G181R, G432A, and D435Y are highly conserved and identified posttranslational modifications sites (PTMs) for proteolytic cleavage and ADP-ribosylation using ConSurf and ModPred servers. The 3D structure of native and mutants was generated using 7 meq as a template from the SwissModeller group, refined by ModRefiner, and validated using the Ramachandran plot. Hence, this paper can be advantageous to understand the association between these missense variants rs12329760, rs781089181, rs762108701, rs1185182900, rs570454392, and rs867186402 and susceptibility to SARS-CoV-2.
人类跨膜丝氨酸蛋白酶 2() 蛋白在前列腺癌的进展中发挥着重要作用。它还通过蛋白水解切割和激活严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的 S 蛋白，促进病毒进入靶细胞。在本研究中，我们使用了不同的可用工具，如 SIFT、PolyPhen2.0、PROVEAN、SNAP2、PMut、MutPred2、I-Mutant Suite、MUpro、iStable、ConSurf、ModPred、SwissModel、PROCHECK、Verify3D 和 TM-align，以识别最具破坏性的变体，并探索其对稳定性、结构和功能的可能影响。通过 SIFT、PolyPhen2.0、PROVEAN、SNAP2 和 PMut 测试的六个错义变体被评估为对蛋白质具有有害影响。此外，V160M、G181R、R240C、P335L、G432A 和 D435Y 变体至少在 2 个服务器中显示出稳定性下降；G181R、G432A 和 D435Y 高度保守，并使用 ConSurf 和 ModPred 服务器识别翻译后修饰（PTM）的蛋白水解切割和 ADP-核糖基化位点。使用 SwissModeller 组的 7meq 作为模板生成天然和突变体的 3D 结构，使用 ModRefiner 进行精修，并使用 Ramachandran 图进行验证。因此，本文有助于理解这些错义变体 rs12329760、rs781089181、rs762108701、rs1185182900、rs570454392 和 rs867186402 与 SARS-CoV-2 易感性之间的关系。
