4qfx: Difference between revisions
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/SAMH1_HUMAN SAMH1_HUMAN]] Putative nuclease involved in innate immune response by acting as a negative regulator of the cell-intrinsic antiviral response. May play a role in mediating proinflammatory responses to TNF-alpha signaling.<ref>PMID:18546154</ref> <ref>PMID:19525956</ref> | [[http://www.uniprot.org/uniprot/SAMH1_HUMAN SAMH1_HUMAN]] Putative nuclease involved in innate immune response by acting as a negative regulator of the cell-intrinsic antiviral response. May play a role in mediating proinflammatory responses to TNF-alpha signaling.<ref>PMID:18546154</ref> <ref>PMID:19525956</ref> | ||
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== Publication Abstract from PubMed == | |||
Sterile alpha motif and Histidine-Aspartate-domain containing protein 1 (SAMHD1) plays a critical role in inhibiting HIV infection, curtailing the pool of dNTPs available for reverse transcription of the viral genome. Recent structural data suggested a compelling mechanism for the regulation of SAMHD1 enzymatic activity, and revealed dGTP-induced association of two inactive dimers into an active tetrameric enzyme. Here, we present the crystal structures of SAMHD1 catalytic core (residues 113-626, SAMHD1c) tetramers, complexed with mixtures of nucleotides, including dGTP/dATP, dGTP/dCTP, dGTP/dTTP, and dGTP/dUTP. The combined structural and biochemical data provide insight into dNTP promiscuity at the secondary allosteric site and how enzymatic activity is modulated. In addition, we present biochemical analyses of GTP-induced SAMHD1 full-length (SAMHD1fl) tetramerization and the structure of SAMHD1c tetramer in complex with GTP/dATP, revealing the structural basis of GTP-mediated SAMHD1 activation. Altogether, the data presented here advance our understanding of SAMHD1 function during cellular homeostasis. | |||
Structural basis of allosteric activation of Sterile Alpha Motif and Histidine-Aspartate Domain containing protein 1 (SAMHD1) by nucleoside triphosphates.,Koharudin LM, Wu Y, DeLucia M, Mehrens J, Gronenborn AM, Ahn J J Biol Chem. 2014 Oct 6. pii: jbc.M114.591958. PMID:25288794<ref>PMID:25288794</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | == References == | ||
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