4X3P
Sirt2 in complex with a myristoyl peptide
4X3P の概要
エントリーDOI | 10.2210/pdb4x3p/pdb |
関連するPDBエントリー | 4X3O |
分子名称 | NAD-dependent protein deacetylase sirtuin-2, peptide PRO-LYS-LYS-THR-GLY, ZINC ION, ... (7 entities in total) |
機能のキーワード | sirt2, myristoyl peptide, hydrolase-peptide complex, hydrolase/peptide |
由来する生物種 | Homo sapiens (Human) 詳細 |
細胞内の位置 | Nucleus. Isoform 1: Cytoplasm . Isoform 2: Cytoplasm . Isoform 5: Cytoplasm : Q8IXJ6 |
タンパク質・核酸の鎖数 | 2 |
化学式量合計 | 35940.68 |
構造登録者 | |
主引用文献 | Wang, Y.,Fung, Y.M.E.,Zhang, W.,He, B.,Chung, M.W.H.,Jin, J.,Hu, J.,Lin, H.,Hao, Q. Deacylation Mechanism by SIRT2 Revealed in the 1'-SH-2'-O-Myristoyl Intermediate Structure. Cell Chem Biol, 24:339-345, 2017 Cited by PubMed Abstract: Sirtuins are NAD-dependent deacylases. Previous studies have established two important enzymatic intermediates in sirtuin-catalyzed deacylation, an alkylamidate intermediate I, which is then converted to a bicyclic intermediate II. However, how intermediate II is converted to products is unknown. Based on potent SIRT2-specific inhibitors we developed, here we report crystal structures of SIRT2 in complexes with a thiomyristoyl lysine peptide-based inhibitor and carba-NAD or NAD. Interestingly, by soaking crystals with NAD, we capture a distinct covalent catalytic intermediate (III) that is different from the previously established intermediates I and II. In this intermediate, the covalent bond between the S and the myristoyl carbonyl carbon is broken, and we believe this intermediate III to be the decomposition product of II en route to form the end products. MALDI-TOF data further support the intermediate III formation. This is the first time such an intermediate has been captured by X-ray crystallography and provides more mechanistic insights into sirtuin-catalyzed reactions. PubMed: 28286128DOI: 10.1016/j.chembiol.2017.02.007 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (1.8 Å) |
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