PTM翻译后修饰.docxVIP

Post-translational modification (PTM) refers to thecovalent and generally enzymatic modification ofproteins after protein biosynthesis.Methylation 甲基化Acetylation 乙酰化Glycosylation 糖基化Lipidation脂化Proteolysis 水解Ubiquitination泛素化Phosphorylation 磷酸化Phosphorylation 磷酸化Phosphoryaltion site: Serine, Threonine, and Tyrosine (mainly)蛋白磷酸化由激酶催化，这一过程是可逆的功能Amplifies signalRegulates protein activity as a switch 可激活可抑制Creates new 激酶可作为药物靶点例如：imatinib（Gleevec）ABL抑制剂Binds to the kinase domain of BCR-ABL in its active conformation and blocks ATP bindingUbiquitination – an important PTMThe biochemistry of ubiquitinationDUB: DeubiquitinatingEnzymeProcessing of Ub Precursors/ Reversal of Ub Conjugation/Editing of Ub Chains/Recycling of UbProteolysis不可逆，剪切蛋白前体，破坏蛋白骨架由protease进行水解分类：based on the catalytic group ivolved in its active siteAsp, Glu protease: 水介导的亲核攻击Ser, Thr, Cys protease: 三价催化蛋白水解能调节蛋白的泛素化和降解The N-end rule: the N-terminal residue of protein determines its half life乙酰化大约80%的真核生物蛋白的乙酰化发生在N末端但是，通常情况下成熟蛋白的N末端并不存在蛋氨酸N-terminal acetylation is catalyzed by MAP and NATMAP: Methionine aminopeptidase - removal of MetNAT: N-terminal acetyltransferase