Structure-function relationships in KDM7 histone demethylases

Shobhit S Chaturvedi; Rajeev Ramanan; Sodiq O Waheed; Tatyana G Karabencheva-Christova; Christo Z Christov

doi:10.1016/bs.apcsb.2019.08.005

Structure-function relationships in KDM7 histone demethylases

Adv Protein Chem Struct Biol. 2019:117:113-125. doi: 10.1016/bs.apcsb.2019.08.005. Epub 2019 Sep 10.

Authors

Shobhit S Chaturvedi¹, Rajeev Ramanan¹, Sodiq O Waheed¹, Tatyana G Karabencheva-Christova¹, Christo Z Christov¹

Affiliation

¹ Department of Chemistry, Michigan Technological University, Houghton, MI, United States.

PMID: 31564306
DOI: 10.1016/bs.apcsb.2019.08.005

Abstract

The demethylation of lysine residues of histone proteins is a key epigenetic mechanism in cells. The enzymes that catalyze these processes are called histone demethylases (KDMs). The largest family of KDMs is the Jumonji C (JmjC) domain-containing enzymes; these includes KDM2-7 subfamily of enzymes. The JmjC proteins are Fe(II) and 2-Oxoglutarate (2OG) - dependent dioxygenases that couple substrate oxidation to decarboxylation of 2OG to form succinate and CO₂. The KDM7 subfamily of enzymes - PHF8 (KDM7B) and KIAA1718 (KDM7A) are human JmjC 2OG-dependent N^ε-methyl lysine demethylases and are involved in demethylation of lysine residues in histones such as H3K27me2/1, H3K9me2/1 and H4K20me1. These enzymes are involved in multiple pathologic processes, including cancers and mental retardation. In this chapter, we present the current state of the art in the structural, biochemical and computational studies of KDM7 enzymes.

Keywords: Histone lysine demethylases; KDM7; Molecular dynamics; QM/MM.

Publication types

Review

MeSH terms

Jumonji Domain-Containing Histone Demethylases / antagonists & inhibitors
Jumonji Domain-Containing Histone Demethylases / chemistry
Jumonji Domain-Containing Histone Demethylases / metabolism*
Models, Molecular
Protein Conformation
Structure-Activity Relationship

Substances

Jumonji Domain-Containing Histone Demethylases