Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	High-resolution structures of the SAMHD1 dGTPase homolog from Leeuwenhoekiella blandensis reveal a novel mechanism of allosteric activation by dATP.
Journal, issue, pages	J Biol Chem, Vol. 298, Issue 7, Page 102073, Year 2022
Publish date	May 26, 2022
Authors	Bradley P Klemm / Andrew P Sikkema / Allen L Hsu / James C Horng / Traci M Tanaka Hall / Mario J Borgnia / Roel M Schaaper /
PubMed Abstract	Deoxynucleoside triphosphate (dNTP) triphosphohydrolases (dNTPases) are important enzymes that may perform multiple functions in the cell, including regulating the dNTP pools and contributing to ...Deoxynucleoside triphosphate (dNTP) triphosphohydrolases (dNTPases) are important enzymes that may perform multiple functions in the cell, including regulating the dNTP pools and contributing to innate immunity against viruses. Among the homologs that are best studied are human sterile alpha motif and HD domain-containing protein 1 (SAMHD1), a tetrameric dNTPase, and the hexameric Escherichia coli dGTPase; however, it is unclear whether these are representative of all dNTPases given their wide distribution throughout life. Here, we investigated a hexameric homolog from the marine bacterium Leeuwenhoekiella blandensis, revealing that it is a dGTPase that is subject to allosteric activation by dATP, specifically. Allosteric regulation mediated solely by dATP represents a novel regulatory feature among dNTPases that may facilitate maintenance of cellular dNTP pools in L. blandensis. We present high-resolution X-ray crystallographic structures (1.80-2.26 Å) in catalytically important conformations as well as cryo-EM structures (2.1-2.7 Å) of the enzyme bound to dGTP and dATP ligands. The structures, the highest resolution cryo-EM structures of any SAMHD1-like dNTPase to date, reveal an intact metal-binding site with the dGTP substrate coordinated to three metal ions. These structural and biochemical data yield insights into the catalytic mechanism and support a conserved catalytic mechanism for the tetrameric and hexameric dNTPase homologs. We conclude that the allosteric activation by dATP appears to rely on structural connectivity between the allosteric and active sites, as opposed to the changes in oligomeric state upon ligand binding used by SAMHD1.
External links	J Biol Chem / PubMed:35643313 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	1.8 - 2.7 Å
Structure data	26126 7tu5 EMDB-26126, PDB-7tu5: Structure of the L. blandensis dGTPase in the apo form Method: EM (single particle) / Resolution: 2.1 Å 26127 7tu6 EMDB-26127, PDB-7tu6: Structure of the L. blandensis dGTPase bound to dATP Method: EM (single particle) / Resolution: 2.7 Å 26128 7tu7 EMDB-26128, PDB-7tu7: Structure of the L. blandensis dGTPase H125A mutant bound to dGTP Method: EM (single particle) / Resolution: 2.5 Å 26129 7tu8 EMDB-26129, PDB-7tu8: Structure of the L. blandensis dGTPase H125A mutant bound to dGTP and dATP Method: EM (single particle) / Resolution: 2.6 Å PDB-7tu0: Structure of the L. blandensis dGTPase bound to Mn Method: X-RAY DIFFRACTION / Resolution: 2.04 Å PDB-7tu1: Structure of the L. blandensis dGTPase R37A mutant Method: X-RAY DIFFRACTION / Resolution: 1.8 Å PDB-7tu2: Structure of the L. blandensis dGTPase R37A mutant bound to Mn Method: X-RAY DIFFRACTION / Resolution: 2.13 Å PDB-7tu3: Structure of the L. blandensis dGTPase del55-58 mutant Method: X-RAY DIFFRACTION / Resolution: 2.17 Å PDB-7tu4: Structure of the L. blandensis dGTPase del55-58 mutant bound to Mn Method: X-RAY DIFFRACTION / Resolution: 2.26 Å
Chemicals	ChemComp-SO4: SULFATE ION / Sulfate ChemComp-MN: Unknown entry ChemComp-HOH: WATER / Water ChemComp-EDO: 1,2-ETHANEDIOL / Ethylene glycol ChemComp-MG: Unknown entry ChemComp-DTP: 2'-DEOXYADENOSINE 5'-TRIPHOSPHATE / Deoxyadenosine triphosphate ChemComp-DGT: 2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE / Deoxyguanosine triphosphate
Source	leeuwenhoekiella blandensis med217 (bacteria) leeuwenhoekiella blandensis (bacteria)
Keywords	HYDROLASE / dGTPase / nucleotide binding