PDBsum entry 1j8f

Gene regulation, transferase

PDB id: 1j8f

Contents

Protein chain

312 a.a. *

Metals

_ZN ×3

Waters ×2598

* Residue conservation analysis

PDB id:

1j8f

Name:

Gene regulation, transferase

Title:

Human sirt2 histone deacetylase

Structure:

Sirtuin 2, isoform 1. Chain: a, b, c. Synonym: sirt2. Sir2-related protein type 2. Silencing information regulator 2-like. Sir2-like 2. Silent mating type information regulation 2, s.Cerevisiae, homolog 2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: sirt2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

1.70Å R-factor: 0.235 R-free: 0.260

Authors:

N.P.Pavletich,M.S.Finnin,J.R.Donigian

Key ref:

M.S.Finnin et al. (2001). Structure of the histone deacetylase SIRT2. Nat Struct Biol, 8, 621-625. PubMed id: 11427894 DOI: 10.1038/89668

Date:

21-May-01 Release date: 06-Jul-01

Protein chains

Q8IXJ6  (SIR2_HUMAN) -  NAD-dependent protein deacetylase sirtuin-2 from Homo sapiens

Seq: 389 a.a.

Struc: 312 a.a.

Enzyme reactions

• Enzyme class 1: E.C.2.3.1.- - ?????
• Enzyme class 2: E.C.2.3.1.286 - protein acetyllysine N-acetyltransferase.
• Reaction: N₆-acetyl-L-lysyl-[protein] + NAD⁺ + H2O = 2''-O-acetyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

Added reference

DOI no: 10.1038/89668

Nat Struct Biol 8:621-625 (2001)

PubMed id: 11427894

Structure of the histone deacetylase SIRT2.

M.S.Finnin, J.R.Donigian, N.P.Pavletich.

ABSTRACT

Sir2 is an NAD-dependent histone deacetylase that mediates transcriptional silencing at mating-type loci, telomeres and ribosomal gene clusters, and has a critical role in the determination of life span in yeast and Caenorhabditis elegans. The 1.7 A crystal structure of the 323 amino acid catalytic core of human SIRT2, a homolog of yeast Sir2, reveals an NAD-binding domain, which is a variant of the Rossmann fold, and a smaller domain composed of a helical module and a zinc-binding module. A conserved large groove at the interface of the two domains is the likely site of catalysis based on mutagenesis. Intersecting this large groove, there is a pocket formed by the helical module. The pocket is lined with hydrophobic residues conserved within each of the five Sir2 classes, suggesting that it is a class-specific protein-binding site.

Selected figure(s)

Figure 3.
Figure 3. Conservation among Sir2-like enzymes. a, Surface representation of SIRT2 generated by the program GRASP39, with residues identical among all Sir2-like enzymes (yellow) and those identical among class I enzymes (magenta) mapped onto the surface. These residues are indicated as ball-and-stick representations in the black-rimmed expansion (right), which shows a close-up view of the potential NAD-binding site. b, An expanded surface representation of the area highlighted in (a) with the hydrophobic residues of the pocket mapped onto the surface in orange. The black-rimmed expansion shows a ribbon diagram of the helical module containing the hydrophobic pocket and ball-and-stick representation of the hydrophobic residues, which are labeled. c, Histone deacetylase activity of the SIRT2 point mutants. Reactions contained wild type or mutant SIRT2, 500 M NAD and 10 g of [3H]acetyl-labeled murine erythroleukemia histone preparation. Assays were performed in triplicate and error bars denote the standard deviation.

Figure 4.
Figure 4. Structural comparison between SIRT2 and Sir2-Af1. a, Superposition of SIRT2 Rossmann fold with Sir2-Af1 in stereo. SIRT2 is shown in cyan and positioned approximately in the same orientation as in Fig. 1 (right), and Sir2-Af1 is in gray. The zinc from SIRT2 is in magenta, whereas the zinc atom from Sir2-Af1 is in orange. The NAD molecule from the Sir2-Af1 -NAD complex is in red. The SIRT2 small pocket and the L-1B loop of Sir2-Af1 are labeled. Notice the increased size of the Sir2-Af1 acetyl-lysine binding site in SIRT2. b, A stereo, close-up view of the NAD binding sites of SIRT2 and Sir2-Af1. The view shows the molecules turned 90° along a horizontal axis in the plane of the paper. Conserved SIRT2 residues that are candidates for NAD-binding or catalysis are shown as ball-and-stick representations and are labeled.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 621-625) copyright 2001.

Figures were selected by an automated process.