The Role of<scp>HATs</scp>and<scp>HDACs</scp>in Cell Physiology and Disease

Santos‐Barriopedro, Irene; Raurell‐Vila, Helena; Vaquero, Alejandro

doi:10.1002/9783527697274.ch4

Cited by 4 publications

(1 citation statement)

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“…Histone acetyltransferases (HATs) and histone deacetylases (HDACs) constitute two groups of enzymes that keep histones acetylated [ 2 ]. Both enzymes have an impact in altering the chromatin’s structure and accessibility to the transcription factors [ 3 ]. Therefore, histone deacetylases (EC 3.5.1.98, HDAC) and acetyltransferases (EC 2.3.1.48, HAT) are enzymes that add and remove the acetyl groups of lysine residues, respectively [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Investigating Potential Cancer Therapeutics: Insight into Histone Deacetylases (HDACs) Inhibitions

Ahmad,

Saeed,

Al-Amery

et al. 2024

Pharmaceuticals

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Histone deacetylases (HDACs) are enzymes that remove acetyl groups from ɛ-amino of histone, and their involvement in the development and progression of cancer disorders makes them an interesting therapeutic target. This study seeks to discover new inhibitors that selectively inhibit HDAC enzymes which are linked to deadly disorders like T-cell lymphoma, childhood neuroblastoma, and colon cancer. MOE was used to dock libraries of ZINC database molecules within the catalytic active pocket of target HDACs. The top three hits were submitted to MD simulations ranked on binding affinities and well-occupied interaction mechanisms determined from molecular docking studies. Inside the catalytic active site of HDACs, the two stable inhibitors LIG1 and LIG2 affect the protein flexibility, as evidenced by RMSD, RMSF, Rg, and PCA. MD simulations of HDACs complexes revealed an alteration from extended to bent motional changes within loop regions. The structural deviation following superimposition shows flexibility via a visual inspection of movable loops at different timeframes. According to PCA, the activity of HDACs inhibitors induces structural dynamics that might potentially be utilized to define the nature of protein inhibition. The findings suggest that this study offers solid proof to investigate LIG1 and LIG2 as potential HDAC inhibitors.

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Section: Introductionmentioning

confidence: 99%