PDBsum entry 3aap

Hydrolase

PDB id: 3aap

Contents

Protein chain

353 a.a. *

Waters ×423

* Residue conservation analysis

PDB id:

3aap

Name:

Hydrolase

Title:

Crystal structure of lp1ntpdase from legionella pneumophila

Structure:

Ectonucleoside triphosphate diphosphohydrolase i. Chain: a. Fragment: unp residues 41-393. Engineered: yes

Source:

Legionella pneumophila. Organism_taxid: 272624. Strain: philadelphia 1. Gene: lpg1905. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.60Å R-factor: 0.189 R-free: 0.207

Authors:

J.P.Vivian,T.Beddoe,J.Rossjohn

Key ref:

J.P.Vivian et al. (2010). Crystal structure of a Legionella pneumophila ecto -triphosphate diphosphohydrolase, a structural and functional homolog of the eukaryotic NTPDases. Structure, 18, 228-238. PubMed id: 20159467

Date:

24-Nov-09 Release date: 09-Feb-10

Protein chain

Q5ZUA2  (Q5ZUA2_LEGPH) -  Ectonucleoside triphosphate diphosphohydrolase I from Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513)

Seq: 393 a.a.

Struc: 353 a.a.*

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

Structure 18:228-238 (2010)

PubMed id: 20159467

Crystal structure of a Legionella pneumophila ecto -triphosphate diphosphohydrolase, a structural and functional homolog of the eukaryotic NTPDases.

J.P.Vivian, P.Riedmaier, H.Ge, J.Le Nours, F.M.Sansom, M.C.Wilce, E.Byres, M.Dias, J.W.Schmidberger, P.J.Cowan, A.J.d'Apice, E.L.Hartland, J.Rossjohn, T.Beddoe.

ABSTRACT

Many pathogenic bacteria have sophisticated mechanisms to interfere with the mammalian immune response. These include the disruption of host extracellular ATP levels that, in humans, is tightly regulated by the nucleoside triphosphate diphosphohydrolase family (NTPDases). NTPDases are found almost exclusively in eukaryotes, the notable exception being their presence in some pathogenic prokaryotes. To address the function of bacterial NTPDases, we describe the structures of an NTPDase from the pathogen Legionella pneumophila (Lpg1905/Lp1NTPDase) in its apo state and in complex with the ATP analog AMPPNP and the subtype-specific NTPDase inhibitor ARL 67156. Lp1NTPDase is structurally and catalytically related to eukaryotic NTPDases and the structure provides a basis for NTPDase-specific inhibition. Furthermore, we demonstrate that the activity of Lp1NTPDase correlates directly with intracellular replication of Legionella within macrophages. Collectively, these findings provide insight into the mechanism of this enzyme and highlight its role in host-pathogen interactions.