5D7O

Crystal structure of Sirt2-ADPR at an improved resolution

5D7O の概要

• エントリーDOI: 10.2210/pdb5d7o/pdb
• 分子名称: NAD-dependent protein deacetylase sirtuin-2, ZINC ION, [(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL [HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL] HYDROGEN PHOSPHATE, ... (5 entities in total)
• 機能のキーワード: hydrolase, human sirt2, deacylase
• 由来する生物種: Homo sapiens (Human)
• 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: 71436.42

構造登録者

Rumpf, T.,Gerhardt, S.,Einsle, O.,Jung, M. (登録日: 2015-08-14, 公開日: 2015-12-02, 最終更新日: 2024-01-10)

主引用文献

Rumpf, T.,Gerhardt, S.,Einsle, O.,Jung, M.
Seeding for sirtuins: microseed matrix seeding to obtain crystals of human Sirt3 and Sirt2 suitable for soaking.
Acta Crystallogr.,Sect.F, 71:1498-1510, 2015

PubMed Abstract: Sirtuins constitute a family of NAD(+)-dependent enzymes that catalyse the cleavage of various acyl groups from the ℇ-amino group of lysines. They regulate a series of cellular processes and their misregulation has been implicated in various diseases, making sirtuins attractive drug targets. To date, only a few sirtuin modulators have been reported that are suitable for cellular research and their development has been hampered by a lack of structural information. In this work, microseed matrix seeding (MMS) was used to obtain crystals of human Sirt3 in its apo form and of human Sirt2 in complex with ADP ribose (ADPR). Crystal formation using MMS was predictable, less error-prone and yielded a higher number of crystals per drop than using conventional crystallization screening methods. The crystals were used to solve the crystal structures of apo Sirt3 and of Sirt2 in complex with ADPR at an improved resolution, as well as the crystal structures of Sirt2 in complex with ADPR and the indoles EX527 and CHIC35. These Sirt2-ADPR-indole complexes unexpectedly contain two indole molecules and provide novel insights into selective Sirt2 inhibition. The MMS approach for Sirt2 and Sirt3 may be used as the basis for structure-based optimization of Sirt2/3 inhibitors in the future.

PubMed: 26625292
DOI: 10.1107/S2053230X15019986

実験手法

X-RAY DIFFRACTION (1.63 Å)