PDBsum entry 2com

Oxidoreductase

PDB id: 2com

Contents

Protein chain

124 a.a. *

* Residue conservation analysis

PDB id:

2com

Name:

Oxidoreductase

Title:

The solution structure of the swirm domain of human lsd1

Structure:

Lysine-specific histone demethylase 1. Chain: a. Fragment: swirm domain. Synonym: amine oxidase flavin containing domain protein 2, aof2 protein, braf35-hdac complex protein bhc110. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: lsd1. Other_details: cell-free protein synthesis

NMR struc:

20 models

Authors:

N.Tochio,T.Umehara,S.Koshiba,M.Inoue,A.Tanaka,T.Kigawa,S.Yokoyama, Riken Structural Genomics/proteomics Initiative (Rsgi)

Key ref:

N.Tochio et al. (2006). Solution structure of the SWIRM domain of human histone demethylase LSD1. Structure, 14, 457-468. PubMed id: 16531230 DOI: 10.1016/j.str.2005.12.004

Date:

18-May-05 Release date: 18-Nov-05

Protein chain

O60341  (KDM1A_HUMAN) -  Lysine-specific histone demethylase 1A from Homo sapiens

Seq: 852 a.a.

Struc: 124 a.a.*

* PDB and UniProt seqs differ at 11 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.1.14.99.66 - [histone-H3]-N(6),N(6)-dimethyl-L-lysine(4) FAD-dependent demethylase.
• Reaction: N₆,N₆-dimethyl-L-lysyl₄-[histone H3] + 2 A + 2 H2O = L-lysyl₄- [histone H3] + 2 formaldehyde + 2 AH2

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

DOI no: 10.1016/j.str.2005.12.004

Structure 14:457-468 (2006)

PubMed id: 16531230

Solution structure of the SWIRM domain of human histone demethylase LSD1.

N.Tochio, T.Umehara, S.Koshiba, M.Inoue, T.Yabuki, M.Aoki, E.Seki, S.Watanabe, Y.Tomo, M.Hanada, M.Ikari, M.Sato, T.Terada, T.Nagase, O.Ohara, M.Shirouzu, A.Tanaka, T.Kigawa, S.Yokoyama.

ABSTRACT

SWIRM is an evolutionarily conserved domain involved in several chromatin-modifying complexes. Recently, the LSD1 protein, which bears a SWIRM domain, was found to be a demethylase for Lys4-methylated histone H3. Here, we report a solution structure of the SWIRM domain of human LSD1. It forms a compact fold composed of 6 alpha helices, in which a 20 amino acid long helix (alpha4) is surrounded by 5 other short helices. The SWIRM domain structure could be divided into the N-terminal part (alpha1-alpha3) and the C-terminal part (alpha4-alpha6), which are connected to each other by a salt bridge. While the N-terminal part forms a SWIRM-specific structure, the C-terminal part adopts a helix-turn-helix (HTH)-related fold. We discuss a model in which the SWIRM domain acts as an anchor site for a histone tail.

Selected figure(s)

Figure 4.
Figure 4. Structural Fold of the N-Terminal SWIRM Part
(A) Conserved residues among the LSD1-type subfamily members. The residues with a ConSurf score greater than 8 are shown in red. The orientation is the same as in Figure 3A. The view on the right is rotated 180° around the z axis from that on the left.
(B) Electrostatic surface. The molecular surface is represented, and it is contoured from negative (red) to positive (blue) potentials. The orientation is the same as the left view in (A).

Figure 7.
Figure 7. Interaction between LSD1-SWIRM and the Peptides of the Histone Sequences
(A–F) Biotinylated peptides were immobilized onto the streptavidin chips, and 64 μM (blue), 32 μM (green), 16 μM (cyan), or 8 μM (magenta) LSD1-SWIRM protein solution was passed over the chip at a 20 μl/min flow rate for 2 min. Biotinylated peptides used are (A) H3(1–20), (B) H3(1–20)-K4diMe, (C) H3(1–20)-K9diMe, (D) H3(1–20)-R8E/T11K, (E) H3(122–135), and (F) H4(1–15). The x axis indicates the time course. Each injection starts at 0 s and ends at 120 s. The y axis indicates the difference in the resonance units between the peptide bound and peptide unbound flow cells.

The above figures are reprinted by permission from Cell Press: Structure (2006, 14, 457-468) copyright 2006.

Figures were selected by an automated process.