PDBsum entry 4kxq

Hydrolase

PDB id: 4kxq

Contents

Protein chains

279 a.a.

26 a.a.

Ligands

APR

BME

GOL

Metals

_ZN

Waters ×300

PDB id:

4kxq

Name:

Hydrolase

Title:

Structure of NAD-dependent protein deacetylase sirtuin-1 (closed state, 1.85 a)

Structure:

NAD-dependent protein deacetylase sirtuin-1. Chain: a. Fragment: deacetylase domain (unp residues 234-510). Synonym: sirt1, hsirt1, regulatory protein sir2 homolog 1, sir2-like protein 1, hsir2. Engineered: yes. NAD-dependent protein deacetylase sirtuin-1. Chain: b. Fragment: unp residues 641-663.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.85Å R-factor: 0.170 R-free: 0.189

Authors:

A.M.Davenport,F.M.Huber,A.Hoelz

Key ref:

A.M.Davenport et al. (2014). Structural and functional analysis of human SIRT1. J Mol Biol, 426, 526-541. PubMed id: 24120939 DOI: 10.1016/j.jmb.2013.10.009

Date:

27-May-13 Release date: 23-Oct-13

Protein chain

Q96EB6  (SIR1_HUMAN) -  NAD-dependent protein deacetylase sirtuin-1 from Homo sapiens

Seq: 747 a.a.

Struc: 279 a.a.*

Protein chain

Q96EB6  (SIR1_HUMAN) -  NAD-dependent protein deacetylase sirtuin-1 from Homo sapiens

Seq: 747 a.a.

Struc: 26 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chains A, B: E.C.2.3.1.- - ?????
• Enzyme class 3: Chains A, B: 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]

N(6)-acetyl-L-lysyl-[protein] + NAD(+) + H2O (Bound ligand (Het Group name = APR) matches with 77.78% similarity) = 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: 10.1016/j.jmb.2013.10.009

J Mol Biol 426:526-541 (2014)

PubMed id: 24120939

Structural and functional analysis of human SIRT1.

A.M.Davenport, F.M.Huber, A.Hoelz.

ABSTRACT

SIRT1 is a NAD(+)-dependent deacetylase that plays important roles in many cellular processes. SIRT1 activity is uniquely controlled by a C-terminal regulatory segment (CTR). Here we present crystal structures of the catalytic domain of human SIRT1 in complex with the CTR in an open apo form and a closed conformation in complex with a cofactor and a pseudo-substrate peptide. The catalytic domain adopts the canonical sirtuin fold. The CTR forms a β hairpin structure that complements the β sheet of the NAD(+)-binding domain, covering an essentially invariant hydrophobic surface. The apo form adopts a distinct open conformation, in which the smaller subdomain of SIRT1 undergoes a rotation with respect to the larger NAD(+)-binding subdomain. A biochemical analysis identifies key residues in the active site, an inhibitory role for the CTR, and distinct structural features of the CTR that mediate binding and inhibition of the SIRT1 catalytic domain.