2xje | pdb_00002xje

CRYSTAL STRUCTURE OF THE D52N VARIANT OF CYTOSOLIC 5'-NUCLEOTIDASE II IN COMPLEX WITH URIDINE 5'-MONOPHOSPHATE AND ADENOSINE TRIPHOSPHATE

spinqualitylabelsall models 2xje, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xje is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ATP, GOL, MG, U5P Related: 2jc9, 2xcv, 2xjd, 2xjf, 2j2c, 2jcm, 2xcx, 2xcw, 2xjb, 2xjc Activity: 5'-nucleotidase, with EC number 3.1.3.5 Resources: FirstGlance, OCA, RCSB, PDBsum Disease [5NTC_HUMAN] Autosomal recessive spastic paraplegia type 45. The disease is caused by mutations affecting the gene represented in this entry. Function [5NTC_HUMAN] May have a critical role in the maintenance of a constant composition of intracellular purine/pyrimidine nucleotides in cooperation with other nucleotidases. Preferentially hydrolyzes inosine 5'-monophosphate (IMP) and other purine nucleotides. Publication Abstract from PubMed Cytosolic 5'-nucleotidase II (cN-II) catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates and participates in the regulation of purine nucleotide pools within the cell. It interferes with the phosphorylation-dependent activation of nucleoside analogues used in the treatment of cancer and viral diseases. It is allosterically activated by a number of phosphate-containing cellular metabolites such as ATP, diadenosine polyphosphates, and 2,3-bisphosphoglycerate, which couple its activity with the metabolic state of the cell. We present seven high-resolution structures of human cN-II, including a ligand-free form and complexes with various substrates and effectors. These structures reveal the structural basis for the allosteric activation of cN-II, uncovering a mechanism where an effector-induced disorder-to-order transition generates rearrangements within the catalytic site and the subsequent coordination of the catalytically essential magnesium. Central to the activation is the large transition of the catalytically essential Asp356. This study also provides the structural basis for the substrate specificity of cN-II, where Arg202, Asp206, and Phe157 seem to be important residues for purine/pyrimidine selectivity. These structures provide a comprehensive structural basis for the design of cN-II inhibitors. They also contribute to the understanding of how the nucleotide salvage pathway is regulated at a molecular level. Structural Basis for the Allosteric Regulation and Substrate Recognition of Human Cytosolic 5'-Nucleotidase II.,Wallden K, Nordlund P J Mol Biol. 2011 May 13;408(4):684-96. Epub 2011 Mar 17. PMID:21396942 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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