PDBsum entry 4cd3

Hydrolase

PDB id: 4cd3

Contents

Protein chain

421 a.a.

Ligands

8E9 ×2

GOL

Waters ×200

PDB id:

4cd3

Name:

Hydrolase

Title:

Rnntpdase2 x4 variant in complex with psb-071

Structure:

Ectonucleoside triphosphate diphosphohydrolase 2. Chain: a. Fragment: ectodomain, residues 28-462. Synonym: ntpdase 2, cd39 antigen-like 1, ecto-atp diphosphohydrolase 2, ecto-atpdase 2, ecto-atpase 2, ntpdase2. Engineered: yes. Mutation: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.19Å R-factor: 0.182 R-free: 0.236

Authors:

M.Zebisch,P.Schaefer,N.Straeter

Key ref:

M.Zebisch et al. (2014). Crystal structure of NTPDase2 in complex with the sulfoanthraquinone inhibitor PSB-071. J Struct Biol, 185, 336-341. PubMed id: 24462745 DOI: 10.1016/j.jsb.2014.01.005

Date:

29-Oct-13 Release date: 12-Feb-14

Protein chain

O35795  (ENTP2_RAT) -  Ectonucleoside triphosphate diphosphohydrolase 2 from Rattus norvegicus

Seq: 495 a.a.

Struc: 421 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.6.1.- - ?????

DOI no: 10.1016/j.jsb.2014.01.005

J Struct Biol 185:336-341 (2014)

PubMed id: 24462745

Crystal structure of NTPDase2 in complex with the sulfoanthraquinone inhibitor PSB-071.

M.Zebisch, Y.Baqi, P.Schäfer, C.E.Müller, N.Sträter.

ABSTRACT

In many vertebrate tissues CD39-like ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) act in concert with ecto-5'-nucleotidase (e5NT, CD73) to convert extracellular ATP to adenosine. Extracellular ATP is a cytotoxic, pro-inflammatory signalling molecule whereas its product adenosine constitutes a universal and potent immune suppressor. Interference with these ectonucleotidases by use of small molecule inhibitors or inhibitory antibodies appears to be an effective strategy to enhance anti-tumour immunity and suppress neoangiogenesis. Here we present the first crystal structures of an NTPDase catalytic ectodomain in complex with the Reactive Blue 2 (RB2)-derived inhibitor PSB-071. In both of the two crystal forms presented the inhibitor binds as a sandwich of two molecules at the nucleoside binding site. One of the molecules is well defined in its orientation. Specific hydrogen bonds are formed between the sulfonyl group and the nucleoside binding loop. The methylphenyl side chain functionality that improved NTPDase2-specificity is sandwiched between R245 and R394, the latter of which is exclusively found in NTPDase2. The second molecule exhibits great in-plane rotational freedom and could not be modelled in a specific orientation. In addition to this structural insight into NTPDase inhibition, the observation of the putative membrane interaction loop (MIL) in two different conformations related by a 10° rotation identifies the MIL as a dynamic section of NTPDases that is potentially involved in regulation of catalysis.