5TD7

Crystal structure of histone deacetylase 10

5TD7 の概要

• エントリーDOI: 10.2210/pdb5td7/pdb
• 分子名称: Zgc:55652, ZINC ION, POTASSIUM ION, ... (7 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Danio rerio (Zebrafish)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 76531.75

構造登録者

Hai, Y.,Shinsky, S.A.,Porter, N.J.,Christianson, D.W. (登録日: 2016-09-17, 公開日: 2017-05-24, 最終更新日: 2023-10-04)

主引用文献

Hai, Y.,Shinsky, S.A.,Porter, N.J.,Christianson, D.W.
Histone deacetylase 10 structure and molecular function as a polyamine deacetylase.
Nat Commun, 8:15368-15368, 2017

PubMed Abstract: Cationic polyamines such as spermidine and spermine are critical in all forms of life, as they regulate the function of biological macromolecules. Intracellular polyamine metabolism is regulated by reversible acetylation and dysregulated polyamine metabolism is associated with neoplastic diseases such as colon cancer, prostate cancer and neuroblastoma. Here we report that histone deacetylase 10 (HDAC10) is a robust polyamine deacetylase, using recombinant enzymes from Homo sapiens (human) and Danio rerio (zebrafish). The 2.85 Å-resolution crystal structure of zebrafish HDAC10 complexed with a transition-state analogue inhibitor reveals that a glutamate gatekeeper and a sterically constricted active site confer specificity for N-acetylspermidine hydrolysis and disfavour acetyllysine hydrolysis. Both HDAC10 and spermidine are known to promote cellular survival through autophagy. Accordingly, this work sets a foundation for studying the chemical biology of autophagy through the structure-based design of inhibitors that may also serve as new leads for cancer chemotherapy.

PubMed: 28516954
DOI: 10.1038/ncomms15368

実験手法

X-RAY DIFFRACTION (2.85 Å)