4cd3

RnNTPDase2 X4 variant in complex with PSB-071RnNTPDase2 X4 variant in complex with PSB-071

Structural highlights 4cd3 is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.19Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ENTP2_RAT In the nervous system, could hydrolyze ATP and other nucleotides to regulate purinergic neurotransmission. Hydrolyzes ADP only to a marginal extent. Publication Abstract from PubMed 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 degrees rotation identifies the MIL as a dynamic section of NTPDases that is potentially involved in regulation of catalysis. Crystal structure of NTPDase2 in complex with the sulfoanthraquinone inhibitor PSB-071.,Zebisch M, Baqi Y, Schafer P, Muller CE, Strater N J Struct Biol. 2014 Jan 21. pii: S1047-8477(14)00006-9. doi:, 10.1016/j.jsb.2014.01.005. PMID:24462745 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ectonucleoside triphosphate diphosphohydrolase

spinqualitylabelsall models 4cd3, resolution 2.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image