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	Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase.
Journal, issue, pages	Nat Commun, Vol. 12, Issue 1, Page 4375, Year 2021
Publish date	Jul 16, 2021
Authors	Colin W Garvie / Xiaoyun Wu / Malvina Papanastasiou / Sooncheol Lee / James Fuller / Gavin R Schnitzler / Steven W Horner / Andrew Baker / Terry Zhang / James P Mullahoo / Lindsay Westlake / Stephanie H Hoyt / Marcus Toetzl / Matthew J Ranaghan / Luc de Waal / Joseph McGaunn / Bethany Kaplan / Federica Piccioni / Xiaoping Yang / Martin Lange / Adrian Tersteegen / Donald Raymond / Timothy A Lewis / Steven A Carr / Andrew D Cherniack / Christopher T Lemke / Matthew Meyerson / Heidi Greulich /
PubMed Abstract	DNMDP and related compounds, or velcrins, induce complex formation between the phosphodiesterase PDE3A and the SLFN12 protein, leading to a cytotoxic response in cancer cells that express elevated ...DNMDP and related compounds, or velcrins, induce complex formation between the phosphodiesterase PDE3A and the SLFN12 protein, leading to a cytotoxic response in cancer cells that express elevated levels of both proteins. The mechanisms by which velcrins induce complex formation, and how the PDE3A-SLFN12 complex causes cancer cell death, are not fully understood. Here, we show that PDE3A and SLFN12 form a heterotetramer stabilized by binding of DNMDP. Interactions between the C-terminal alpha helix of SLFN12 and residues near the active site of PDE3A are required for complex formation, and are further stabilized by interactions between SLFN12 and DNMDP. Moreover, we demonstrate that SLFN12 is an RNase, that PDE3A binding increases SLFN12 RNase activity, and that SLFN12 RNase activity is required for DNMDP response. This new mechanistic understanding will facilitate development of velcrin compounds into new cancer therapies.
External links	Nat Commun / PubMed:34272366 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	1.7 - 3.22 Å
Structure data	23494 7lrc EMDB-23494, PDB-7lrc: Cryo-EM of the SLFN12-PDE3A complex: PDE3A body refinement Method: EM (single particle) / Resolution: 2.97 Å 23495 7lrd EMDB-23495, PDB-7lrd: Cryo-EM of the SLFN12-PDE3A complex: Consensus subset model Method: EM (single particle) / Resolution: 3.22 Å 23496 7lre EMDB-23496, PDB-7lre: Cryo-EM of the SLFN12-PDE3A complex: SLFN12 body refinement Method: EM (single particle) / Resolution: 2.76 Å PDB-7kwe: Crystal structure of the catalytic domain of human PDE3A bound to DNMDP Method: X-RAY DIFFRACTION / Resolution: 2.0 Å PDB-7l27: Crystal structure of the catalytic domain of human PDE3A Method: X-RAY DIFFRACTION / Resolution: 1.7 Å PDB-7l28: Crystal structure of the catalytic domain of human PDE3A bound to Trequinsin Method: X-RAY DIFFRACTION / Resolution: 2.2 Å PDB-7l29: Crystal structure of the catalytic domain of human PDE3A bound to AMP Method: X-RAY DIFFRACTION / Resolution: 2.08 Å
Chemicals	ChemComp-X5M: (4~{R})-3-[4-(diethylamino)-3-[oxidanyl(oxidanylidene)-$l^{4}-azanyl]phenyl]-4-methyl-4,5-dihydro-1~{H}-pyridazin-6-one ChemComp-MN: Unknown entry ChemComp-MG: Unknown entry ChemComp-ACT: ACETATE ION / Acetate ChemComp-HOH: WATER / Water ChemComp-CA: Unknown entry ChemComp-XKG: (2E)-9,10-dimethoxy-3-methyl-2-[(2,4,6-trimethylphenyl)imino]-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one / inhibitorYM / Trequinsin ChemComp-AMP: ADENOSINE MONOPHOSPHATE / AMPYM / Adenosine monophosphate ChemComp-ZN: Unknown entry
Source	homo sapiens (human)
Keywords	HYDROLASE / HYDROLASE/HYDROLASE INHIBITOR / HYDROLASE-HYDROLASE INHIBITOR complex / complex / velcrin / molecular glue / DNMDP / RNA BINDING PROTEIN