Structural highlights
5td7 is a 1 chain structure with sequence from Danio rerio. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | X-ray diffraction, Resolution 2.85Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
HDA10_DANRE Polyamine deacetylase (PDAC), which acts preferentially on N(8)-acetylspermidine, and also on acetylcadaverine and acetylputrescine (PubMed:28516954). Exhibits attenuated catalytic activity toward N(1),N(8)-diacetylspermidine and very low activity, if any, toward N(1)-acetylspermidine (PubMed:28516954). Has a very weak lysine deacetylase, if any (PubMed:28516954).[1]
Publication Abstract from PubMed
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 A-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 N8-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.
Histone deacetylase 10 structure and molecular function as a polyamine deacetylase.,Hai Y, Shinsky SA, Porter NJ, Christianson DW Nat Commun. 2017 May 18;8:15368. doi: 10.1038/ncomms15368. PMID:28516954[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hai Y, Shinsky SA, Porter NJ, Christianson DW. Histone deacetylase 10 structure and molecular function as a polyamine deacetylase. Nat Commun. 2017 May 18;8:15368. doi: 10.1038/ncomms15368. PMID:28516954 doi:http://dx.doi.org/10.1038/ncomms15368
- ↑ Hai Y, Shinsky SA, Porter NJ, Christianson DW. Histone deacetylase 10 structure and molecular function as a polyamine deacetylase. Nat Commun. 2017 May 18;8:15368. doi: 10.1038/ncomms15368. PMID:28516954 doi:http://dx.doi.org/10.1038/ncomms15368
