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Ligand‐induced transition in conformations of vicinal cysteine disulfides in proteins
Proteins: Structure, Function, and Bioinformatics ( IF 2.9 ) Pub Date : 2020-12-30 , DOI: 10.1002/prot.26039
K Kasi Amarnath Reddy 1 , Muddagoni Jayashree 1 , Panchada Ch V Govindu 1 , Konkallu Hanumae Gowd 1
Affiliation  

Vicinal cysteine disulfides are thought to be associated with specific conformations of cysteine disulfides due to the restricted rotation of single bonds in an eight‐membered cyclic disulfide loop. Conformations of vicinal cysteine disulfides are analyzed using χ1, χ2, χ3, χ2', χ1' torsion angles in the crystal structures of proteins retrieved from Protein Data Bank (PDB). 85% of vicinal disulfides have (+, −)LHStaple conformation with trans configuration of the peptide bond and 9% have (−, −)RHStaple conformation with cis configured peptide bond. Conformational analysis of dipeptide Cys‐Cys vicinal disulfide by density functional theory (DFT) further supported (+, −)LHStaple, (−, −)RHStaple, and (+, +)RHStaple as the preferred conformations of vicinal disulfides. Interestingly, the rare conformations of vicinal disulfides are observed in the ligand‐bound forms of proteins and have higher disulfide strain energy. Conformations of vicinal disulfides in palmitoyl protein thioesterase 1, AChBP, and α7 nicotinic receptor are changed from preferred (+, −)LHStaple to rare (+, −)AntiLHHook/(+, −)AntiRHHook/(+, +)RHStaple conformation due to binding of ligands. Surprisingly, ligands are proximal to the vicinal disulfides in protein complexes that exhibited rare conformations of vicinal disulfides. The report has identified (+, −) LHStaple/(−, −) RHStaple as the hallmark conformations of vicinal disulfides and unraveled ligand‐induced transition in conformations of vicinal cysteine disulfides in proteins.

中文翻译:

配体诱导的蛋白质中邻位半胱氨酸二硫化物的构象转变

由于八元环二硫醚环中单键的旋转受限,邻位半胱氨酸二硫化物被认为与半胱氨酸二硫化物的特定构象有关。使用 χ 1 , χ 2 , χ 3 , χ 2 ', χ 1分析邻位半胱氨酸二硫化物的构象' 从蛋白质数据库 (PDB) 检索的蛋白质晶体结构中的扭转角。85% 的邻位二硫化物具有 (+, -)LHStaple 构象和反式肽键构象,9% 具有 (-, -)RHStaple 构象和顺式肽键。通过密度泛函理论 (DFT) 对二肽 Cys-Cys 邻二硫化物的构象分析进一步支持 (+, -)LHStaple、(-, -)RHStaple 和 (+, +)RHStaple 作为邻位二硫化物的优选构象。有趣的是,在蛋白质的配体结合形式中观察到连位二硫化物的罕见构象,并且具有更高的二硫化物应变能。棕榈酰蛋白硫酯酶 1、AChBP 和 α7 烟碱受体中连位二硫化物的构象从优选的 (+, -)LHStaple 变为罕见的 (+, -)AntiLHHook/(+, -)AntiRHHook/(+, +)由于配体结合导致的RHStaple构象。令人惊讶的是,配体与蛋白质复合物中的邻二硫化物相邻,这些蛋白质复合物中表现出罕见的邻二硫化物构象。该报告已将 (+, -) LHStaple/(-, -) RHStaple 确定为邻位二硫化物的标志性构象和蛋白质中邻位半胱氨酸二硫化物构象中未解开的配体诱导转变。
更新日期:2020-12-30
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