2j2c
CRYSTAL STRUCTURE OF HUMAN CYTOSOLIC 5'-NUCLEOTIDASE II (NT5C2, CN-II)CRYSTAL STRUCTURE OF HUMAN CYTOSOLIC 5'-NUCLEOTIDASE II (NT5C2, CN-II)
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCytosolic 5'-nucleotidase II catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates and regulates the IMP and GMP pools within the cell. It possesses phosphotransferase activity and thereby also catalyzes the reverse reaction. Both reactions are allosterically activated by adenine-based nucleotides and 2,3-bisphosphoglycerate. We have solved structures of cytosolic 5'-nucleotidase II as native protein (2.2 Angstrom) and in complex with adenosine (1.5 Angstrom) and beryllium trifluoride (2.15 Angstrom) The tetrameric enzyme is structurally similar to enzymes of the haloacid dehalogenase (HAD) superfamily, including mitochondrial 5'(3')-deoxyribonucleotidase and cytosolic 5'-nucleotidase III but possesses additional regulatory regions that contain two allosteric effector sites. At effector site 1 located near a subunit interface we modeled diadenosine tetraphosphate with one adenosine moiety in each subunit. This efficiently glues the tetramer subunits together in pairs. The model shows why diadenosine tetraphosphate but not diadenosine triphosphate activates the enzyme and supports a role for cN-II during apoptosis when the level of diadenosine tetraphosphate increases. We have also modeled 2,3-bisphosphoglycerate in effector site 1 using one phosphate site from each subunit. By comparing the structure of cytosolic 5'-nucleotidase II with that of mitochondrial 5'(3')-deoxyribonucleotidase in complex with dGMP, we identified residues involved in substrate recognition. Crystal structure of human cytosolic 5'-nucleotidase II: insights into allosteric regulation and substrate recognition.,Wallden K, Stenmark P, Nyman T, Flodin S, Graslund S, Loppnau P, Bianchi V, Nordlund P J Biol Chem. 2007 Jun 15;282(24):17828-36. Epub 2007 Apr 3. PMID:17405878[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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