9RJD

X-ray structure of Leptospira interrogans Histone deacetylase 11 (HDAC11) in complex with cis-dodec-5-enoic acid

This is a non-PDB format compatible entry.

Summary for 9RJD

• Entry DOI: 10.2210/pdb9rjd/pdb
• Descriptor: Histone deacetylase, GLYCEROL, (Z)-dodec-5-enoic acid, ... (9 entities in total)
• Functional Keywords: histone deacetylase 11, leptospira interrogans, class iv hdac, zinc binding group, hydrolase
• Biological source: Leptospira interrogans
• Total number of polymer chains: 2
• Total formula weight: 71093.10

Authors

Novakova, Z.,Schenkmayerova, A.,Motlova, L.,Barinka, C. (deposition date: 2025-06-12, release date: 2026-06-24, Last modification date: 2026-07-22)

Primary citation

Novakova, Z.,Bartosova-Sojkova, P.,Kudlacova, J.,Baselious, F.,Kutilova, Z.,Jaklova, P.,Meleshin, M.,Motlova, L.,Schenkmayerova, A.,Vrkoslav, V.,Strnad, S.,Horacek, N.,Gruber, A.,Zacek, P.,Kroll, S.,Havlinova, B.,Ondrakova, M.,Tuckova, R.,Krunclova, T.,Cvacka, J.,Obornik, M.,Schutkowski, M.,Sippl, W.,Barinka, C.
Functional divergence and structural changes of Class IV histone deacetylases (HDACs) across the tree of life.
Mol.Biol.Evol., 43:-, 2026

PubMed Abstract: Class IV histone deacetylases (HDACs) are the least understood branch of the classical zinc-dependent HDAC family with HDAC11 standing out as the sole member of Class IV HDACs. Using a broad phylogenetic dataset spanning bacteria, archaea, and eukaryotes, we identified two deeply conserved HDAC11 lineages, clades A and B, that differ in evolutionary origin, predicted subcellular localization, and enzymatic properties. Clade A is enriched in phototrophic eukaryotes and targeted to mitochondria or plastids, whereas clade B predominates in heterotrophs and localizes mainly to the cytoplasm or nucleus. High-resolution crystal structures of selected representatives from each clade revealed a conserved catalytic core but distinct structural features-including electrostatic surface profiles, loop architectures, and foot pocket geometries-that clearly separate the two lineages and act as sequential "selectivity filters" shaping substrate specificity. Biochemical assays show robust long-chain fatty acid deacylase activity in clade B enzymes, but no detectable activity for any of clade A representatives against peptide substrates, suggesting adaptation to alternative, nonpeptidic targets. Together, these findings define a revised evolutionary framework for HDAC11 and provide structural and functional insights into the diversification of this ancient enzyme family.

PubMed: 42308148
DOI: 10.1093/molbev/msag150

Experimental method

X-RAY DIFFRACTION (1.51 Å)