5TD7
Crystal structure of histone deacetylase 10
Summary for 5TD7
| Entry DOI | 10.2210/pdb5td7/pdb |
| Descriptor | Zgc:55652, ZINC ION, POTASSIUM ION, ... (7 entities in total) |
| Functional Keywords | hydrolase |
| Biological source | Danio rerio (Zebrafish) |
| Total number of polymer chains | 1 |
| Total formula weight | 76531.75 |
| Authors | Hai, Y.,Shinsky, S.A.,Porter, N.J.,Christianson, D.W. (deposition date: 2016-09-17, release date: 2017-05-24, Last modification date: 2023-10-04) |
| Primary citation | 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 Cited by 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: 28516954DOI: 10.1038/ncomms15368 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.85 Å) |
Structure validation
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