OAS1 produces oligoadenylates

Stable Identifier
Reaction [transition]
Homo sapiens
Related Species
Tick-borne encephalitis virus, Dengue virus, West Nile virus
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Oligoadenylate synthetase 1 (OAS1) produces the second messenger 5’-triphosphorylated 2'-5'-oligoadenylate (2-5A), which limits viral propagation through the activation of the enzyme RNase L (reviewed by Silverman RH 2007; Hornung V et al. 2014). OAS1 produces 2-5A from ATP by transferring an AMP unit from the AMP donor substrate (ATP) to the 2′-hydroxyl group of an AMP acceptor substrate, ATP or a preformed 2-5A oligomer (Lohofener J et al. 2015). This produces a 2-5A dimer (ppp5'A(2'-5')A) or an elongated 2-5A oligomer (ppp5'A((2'-5')A)n), as well as one molecule of pyrophosphate (PPi) for each AMP residue added (Lohofener J et al. 2015). Structural studies showed that RNA-induced conformational rearrangement in OAS1 positions the active site residues D75, D77, and D148 compactly for coordination of two Mg2+ ions and for binding of ATP (Donovan J et al. 2013). The assembly of this critical active-site structure of OAS1 provides the gate that couples binding of dsRNA to the production and downstream functions of 2-5A, enabling OAS1 to function as a sensor of double-stranded RNA (dsRNA) (Donovan J et al. 2013).

Literature References
PubMed ID Title Journal Year
23319625 Structural basis for cytosolic double-stranded RNA surveillance by human oligoadenylate synthetase 1

Korennykh, A, Dufner, M, Donovan, J

Proc. Natl. Acad. Sci. U.S.A. 2013
25892109 The Activation Mechanism of 2'-5'-Oligoadenylate Synthetase Gives New Insights Into OAS/cGAS Triggers of Innate Immunity

Kay-Fedorov, P, Manstein, DJ, Fedorov, R, Lohöfener, J, Steinke, N, Baruch, P, Tishchenko, S, Nikulin, A

Structure 2015
Catalyst Activity

2'-5'-oligoadenylate synthetase activity of OAS1 tetramer:OAS1 ligand [cytosol]

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