Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases

Structure
John R SomozaLeslie W Tari

Abstract

Modulation of the acetylation state of histones plays a pivotal role in the regulation of gene expression. Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysines near the N termini of histones. This reaction promotes the condensation of chromatin, leading to repression of transcription. HDAC deregulation has been linked to several types of cancer, suggesting a potential use for HDAC inhibitors in oncology. Here we describe the first crystal structures of a human HDAC: the structures of human HDAC8 complexed with four structurally diverse hydroxamate inhibitors. This work sheds light on the catalytic mechanism of the HDACs, and on differences in substrate specificity across the HDAC family. The structure also suggests how phosphorylation of Ser39 affects HDAC8 activity.

References

Oct 10, 1996·Nature·Z F KanyoD W Christianson
Apr 16, 1998·Genes & Development·K Struhl
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·V M RichonP A Marks
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·C A HassigS L Schreiber
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Mar 25, 1999·Acta Crystallographica. Section D, Biological Crystallography·C R KissingerD B Fogel
Mar 1, 2000·Trends in Biochemical Sciences·H H Ng, A Bird
Aug 3, 2000·FEBS Letters·I Van den WyngaertS U Kass
Aug 6, 2000·The Biochemical Journal·J J BuggyJ M Clark
Mar 16, 2001·Current Opinion in Genetics & Development·S KhochbinD Seigneurin-Berny
Oct 24, 2001·Current Opinion in Oncology·P A MarksR A Rifkind
Mar 27, 2002·Anti-cancer Drugs·David M Vigushin, R Charles Coombes
Apr 19, 2002·The Journal of Biological Chemistry·Gregory DavidRonald A DePinho
Apr 27, 2002·Acta Crystallographica. Section D, Biological Crystallography·Marjorie M Harding
Jun 26, 2002·The Journal of Biological Chemistry·Shih-Chang Tsai, Edward Seto
Jul 18, 2002·Nature Reviews. Drug Discovery·Ricky W Johnstone
Jan 2, 2003·Molecular and Cellular Biology·Kristie L DurstScott W Hiebert
Feb 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Emma HocklyGillian P Bates
Jan 1, 2004·Molecular and Cellular Biology·Heehyoung LeeEdward Seto
Nov 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·E A Merritt, M E Murphy
Jul 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·A PerrakisV S Lamzin
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

❮ Previous
Next ❯

Citations

Jan 17, 2014·Physical Chemistry Chemical Physics : PCCP·Subha Kalyaanamoorthy, Yi-Ping Phoebe Chen
May 1, 2012·Pharmaceutical Patent Analyst·Sophia N OnonyeDennis L Wright
Oct 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·A LahmP Gallinari
Oct 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Alessandro VanniniStefania Di Marco
Jan 3, 2014·The Journal of Clinical Investigation·Alison C West, Ricky W Johnstone
Aug 22, 2013·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·W K YuM S Yang
Jun 4, 2014·Applied Biochemistry and Biotechnology·Yudibeth Sixto-LópezJosé Correa-Basurto
Sep 13, 2013·Future Medicinal Chemistry·Michel WeïwerEdward B Holson
Oct 17, 2014·Cell Death & Disease·Y KangR H Dashwood
Nov 17, 2006·Nature Chemical Biology·Ian Collins, Paul Workman
Oct 7, 2006·BMC Biochemistry·Nayana KamathMary Kay H Pflum
Apr 3, 2007·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Tine Kragh NielsenRalf Ficner
Jan 24, 2008·Antimicrobial Agents and Chemotherapy·K T AndrewsD P Fairlie
Feb 23, 2008·Nature Reviews. Molecular Cell Biology·Xiang-Jiao Yang, Edward Seto
Mar 25, 2008·Cellular and Molecular Life Sciences : CMLS·D P DowlingD W Christianson
Jun 24, 2008·Chemical Society Reviews·Anton V Bieliauskas, Mary Kay H Pflum
Jul 11, 2008·The Journal of Biological Chemistry·Matthew J BottomleyAndrea Carfí
Dec 20, 2008·Journal of Medicinal Chemistry·Adegboyega K OyelereYuhong Fan
Oct 27, 2009·Nature Reviews. Drug Discovery·Liqing WangWayne W Hancock
Dec 24, 2009·The Journal of Biological Chemistry·Stephanie L GanttCarol A Fierke
Jul 10, 2010·Journal of the American Chemical Society·Kyle V ButlerAlan P Kozikowski
Jul 31, 2010·Journal of Medicinal Chemistry·Sandra C MwakwariAdegboyega K Oyelere
Oct 6, 2010·Antioxidants & Redox Signaling·Anthony R Cyr, Frederick E Domann
Apr 5, 2011·Journal of the American Chemical Society·Ruibo WuYingkai Zhang
Apr 18, 2012·Antimicrobial Agents and Chemotherapy·Subathdrage D M SumanadasaKatherine T Andrews
Dec 5, 2012·PloS One·Sundarapandian ThangapandianKeun Woo Lee

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.