PDBsum entry 3pdh

Hydrolase

PDB id: 3pdh

Contents

Protein chains

237 a.a. *

13 a.a. *

Metals

_ZN

Waters ×247

* Residue conservation analysis

PDB id:

3pdh

Name:

Hydrolase

Title:

Structure of sir2tm bound to a propionylated peptide

Structure:

NAD-dependent deacetylase. Chain: a. Synonym: regulatory protein sir2 homolog. Engineered: yes. Cellular tumor antigen p53 18-residue peptide. Chain: d. Synonym: antigen ny-co-13, phosphoprotein p53, tumor suppressor p53. Engineered: yes

Source:

Thermotoga maritima. Organism_taxid: 2336. Gene: npda, sir2, tm_0490. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: chemically synthesized propionylated p53 peptide

Resolution:

1.80Å R-factor: 0.167 R-free: 0.210

Authors:

C.Wolberger,P.Bheda

Key ref:

P.Bheda et al. (2011). Structure of Sir2Tm bound to a propionylated peptide. Protein Sci, 20, 131-139. PubMed id: 21080423

Date:

22-Oct-10 Release date: 19-Jan-11

Protein chain

Q9WYW0  (NPD_THEMA) -  NAD-dependent protein deacetylase from Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8)

Seq: 246 a.a.

Struc: 237 a.a.

Protein chain

P04637  (P53_HUMAN) -  Cellular tumor antigen p53 from Homo sapiens

Seq: 393 a.a.

Struc: 13 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: Chain A: 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]
• Enzyme class 2: Chain D: E.C.?

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

Protein Sci 20:131-139 (2011)

PubMed id: 21080423

Structure of Sir2Tm bound to a propionylated peptide.

P.Bheda, J.T.Wang, J.C.Escalante-Semerena, C.Wolberger.

ABSTRACT

Lysine propionylation is a recently identified post-translational modification that has been observed in proteins such as p53 and histones and is thought to play a role similar to acetylation in modulating protein activity. Members of the sirtuin family of deacetylases have been shown to have depropionylation activity, although the way in which the sirtuin catalytic site accommodates the bulkier propionyl group is not clear. We have determined the 1.8 Å structure of a Thermotoga maritima sirtuin, Sir2Tm, bound to a propionylated peptide derived from p53. A comparison with the structure of Sir2Tm bound to an acetylated peptide shows that hydrophobic residues in the active site shift to accommodate the bulkier propionyl group. Isothermal titration calorimetry data show that Sir2Tm binds propionylated substrates more tightly than acetylated substrates, but kinetic assays reveal that the catalytic rate of Sir2Tm deacylation of propionyl-lysine is slightly reduced to acetyl-lysine. These results serve to broaden our understanding of the newly identified propionyl-lysine modification and the ability of sirtuins to depropionylate, as well as deacetylate, substrates.