Zhang Yuan, Yang Ru, Huang Juan, Liang Qiujin, Guo Yanmin, Bian Weixiang, Luo Lingfei, Li Hongtao
The State Key Laboratory Breeding Base of Bioresources and Eco-environments, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China.
The State Key Laboratory Breeding Base of Bioresources and Eco-environments, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China.
FEBS Lett. 2015 Nov 30;589(23):3648-53. doi: 10.1016/j.febslet.2015.10.025. Epub 2015 Oct 28.
The phosphothreonine lyases OspF and SpvC irreversibly inactivate host dual-phosphorylated mitogen-activated protein kinases (MAPKs) [pThr-X-pTyr motif] through β-elimination. We found that dual-phosphorylated (pSer-X-pTyr) MAPK substrate peptides and their resulting catalytic products cross-link to OspF and SpvC. Mass spectrometry results revealed that these linkages form between lysine, which acts as a general base, and dehydroalanine (Dha) on catalytic products. The nucleophilic addition efficiency is dependent on the K136 residue being in a deprotonated state. Peptide cross-linking inhibits the activity of SpvC and blocks the inactivation of MAPK signaling by SpvC. Small compounds mimicking these sequences may act as phosphothreonine lyase inhibitors.
磷酸苏氨酸裂解酶OspF和SpvC通过β-消除反应不可逆地使宿主双磷酸化的丝裂原活化蛋白激酶（MAPKs）[pThr-X-pTyr基序]失活。我们发现双磷酸化（pSer-X-pTyr）的MAPK底物肽及其产生的催化产物与OspF和SpvC发生交联。质谱结果表明，这些连接形成于作为通用碱的赖氨酸与催化产物上的脱氢丙氨酸（Dha）之间。亲核加成效率取决于K136残基处于去质子化状态。肽交联抑制SpvC的活性，并阻断SpvC对MAPK信号传导的失活作用。模拟这些序列的小分子化合物可能充当磷酸苏氨酸裂解酶抑制剂。
