Preparation of a new construct of human histone deacetylase 8 for the crystallization of enzyme-inhibitor complexes.
Crystallization
/ methods
Crystallography, X-Ray
/ methods
Drug Design
Histone Deacetylase Inhibitors
/ chemistry
Histone Deacetylases
/ chemistry
Humans
Models, Molecular
Peptides
/ chemistry
Protein Conformation
/ drug effects
Protein Multimerization
/ drug effects
Repressor Proteins
/ antagonists & inhibitors
Drug design
Epigenetics
Protein crystallography
Zinc enzyme
Journal
Methods in enzymology
ISSN: 1557-7988
Titre abrégé: Methods Enzymol
Pays: United States
ID NLM: 0212271
Informations de publication
Date de publication:
2019
2019
Historique:
entrez:
14
10
2019
pubmed:
14
10
2019
medline:
3
6
2020
Statut:
ppublish
Résumé
The metal-dependent histone deacetylases (HDACs) are critical regulatory enzymes that modulate myriad cellular processes. Implicated in cancer, neurodegenerative diseases, and other clinical disorders, various HDAC isozymes serve as validated drug targets. However, structural similarities among the HDAC isozymes challenge efforts in targeting a single isozyme for therapeutic intervention with an inhibitor. X-ray crystallography remains the premiere technique for studying the chemistry of isozyme-selective inhibition. While crystal structures of many HDAC-inhibitor complexes have been determined, especially with the class I isozyme HDAC8, the study of complexes with large inhibitors is complicated by flexible regions of the protein structure that can hinder crystallization. Here, we outline an approach for the identification of regions in HDAC8 that may hinder crystallization. We also describe protocols for the design and preparation of a truncated HDAC8 construct, HDAC8
Identifiants
pubmed: 31606091
pii: S0076-6879(19)30279-4
doi: 10.1016/bs.mie.2019.06.029
pmc: PMC6941479
mid: NIHMS1064074
pii:
doi:
Substances chimiques
Histone Deacetylase Inhibitors
0
Peptides
0
Repressor Proteins
0
trapoxin A
133155-89-2
HDAC8 protein, human
EC 3.5.1.98
Histone Deacetylases
EC 3.5.1.98
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
561-585Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM049758
Pays : United States
Informations de copyright
© 2019 Elsevier Inc. All rights reserved.
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