New molecular interaction of IIANtr and HPr from Burkholderia pseudomallei identified by X‐ray crystallography and docking studies1. Issue 9 (23rd August 2013)

• Record Type: Journal Article
• Authors: Kim, Mi‐Sun; Lee, Hasup; Heo, Lim; Lim, Areum; Seok, Chaok; Shin, Dong Hae
• Is Part Of: Proteins. Volume 81:Issue 9(2013)
• Page Start: 1499
• Page End: 1508
• Publication Date: 2013-08-23
• Subjects: Proteins -- Periodicals; Proteins -- Periodicals; 572.6
• DOI: 10.1002/prot.24275
• Languages: English
• ISSNs: 0887-3585

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The nitrogen‐related phosphoenolpyruvate phosphotransferase system (PTS<sup>Ntr</sup>) is involved in controlling ammonia assimilation and nitrogen fixation. The additional role of PTS<sup>Ntr</sup> as a regulatory link between nitrogen and carbon utilization in <italic>Escherichia coli</italic> is assumed to be closely related to molecular functions of IIA<sup>Ntr</sup> in potassium homeostasis. We have determined the crystal structure of IIA<sup>Ntr</sup> from <italic>Burkholderia pseudomallei</italic> (<italic>Bp</italic>IIA<sup>Ntr</sup>), which is a causative agent of melioidosis. The crystal structure of dimeric <italic>Bp</italic>IIA<sup>Ntr</sup> determined at 3.0 Å revealed that its active sites are mutually blocked. This dimeric state is stabilized by charge and weak hydrophobic interactions. Overall monomeric structure and the active site residues, Arg51 and His67, of <italic>Bp</italic>IIA<sup>Ntr</sup> are well conserved with those of IIA<sup>Ntr</sup> enzymes from <italic>E. coli</italic> and <italic>Neisseria meningitides</italic>. Interestingly, His113 of <italic>Bp</italic>IIA<sup>Ntr</sup>, which corresponds to a key residue in another phosphoryl group relay in the mannitol‐specific enzyme EIIA family (EIIA<sup>Mtl</sup>), is located away from the active site due to the loop connecting β5 and α3. Combined with other differences in molecular surface properties, these structural signatures distinguish the IIA<sup>Ntr</sup> family from the EIIA<sup>Mtl</sup> family. Since, there is no gene for NPr in the chromosome of <italic>B. pseudomallei</italic>, modeling and docking studies of the <italic>Bp</italic>IIA<sup>Ntr</sup>–<italic>Bp</italic>HPr complex has been performed to support the proposal on the NPr‐like activity of <italic>Bp</italic>HPr. A potential dual role of <italic>Bp</italic>HPr as a nonspecific phosphocarrier protein interacting with both sugar EIIAs and IIA<sup>Ntr</sup> in <italic>B. pseudomallei</italic> has been discussed. Proteins 2013. © 2013 Wiley Periodicals, Inc.</p> </abstract>