6f4x

Crystal structure of H. pylori purine nucleoside phosphorylase in complex with PO4 and formycin A

spinqualitylabelsall models 6f4x, resolution 1.69Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6f4x is a 6 chain structure with sequence from Atcc 43504. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, FMC, PO4 Related: 5lu0, 6f4w Gene: deoD, HP_1178 (ATCC 43504) Activity: Purine-nucleoside phosphorylase, with EC number 2.4.2.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Even with decades of research, purine nucleoside phosphorylases (PNPs) are enzymes whose mechanism is yet to be fully understood. This is especially true in the case of hexameric PNPs, and is probably, in part, due to their complex oligomeric nature and a whole spectrum of active site conformations related to interactions with different ligands. Here we report an extensive structural characterization of the apo forms of hexameric PNP from Helicobacter pylori (HpPNP), as well as its complexes with phosphate (Pi ) and an inhibitor, formycin A (FA), together with kinetic, binding, docking and molecular dynamics studies. X-ray structures show previously unseen distributions of open and closed active sites. Microscale thermophoresis results indicate that a two-site model describes Pi binding, while a three-site model is needed to characterize FA binding, irrespective of Pi presence. The latter may be related to the newly found non-standard mode of FA binding. The ternary complex of the enzyme with Pi and FA shows, however, that Pi binding stabilizes the standard mode of FA binding. Surprisingly, HpPNP has low affinity towards the natural substrate adenosine. Molecular dynamics simulations show that Pi moves out of most active sites, in accordance with its weak binding. Conformational changes between non-standard and standard binding modes of nucleoside are observed during the simulations. Altogether, these findings show some unique features of HpPNP and provide new insights into the functioning of the active sites, with implications for understanding the complex mechanism of catalysis of this enzyme. This article is protected by copyright. All rights reserved. Helicobacter pylori purine nucleoside phosphorylase shows new distribution patterns of open and closed active site conformations and unusual biochemical features.,Narczyk M, Bertosa B, Papa L, Vukovic V, Lescic Asler I, Wielgus-Kutrowska B, Bzowska A, Luic M, Stefanic Z FEBS J. 2018 Feb 12. doi: 10.1111/febs.14403. PMID:29430816 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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