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4rwn

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Revision as of 09:51, 1 May 2019

Crystal structure of the pre-reactive state of porcine OAS1

Structural highlights

4rwn is a 3 chain structure with sequence from Pig. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4rwq, 4rwo, 4rwp
Gene:	OAS1 (PIG)
Activity:	2'-5' oligoadenylate synthase, with EC number 2.7.7.84
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[OAS1_PIG] Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. The secreted form displays antiviral effect against vesicular stomatitis virus (VSV), herpes simplex virus type 2 (HSV-2), and encephalomyocarditis virus (EMCV) and stimulates the alternative antiviral pathway independent of RNase L.^[1]

Publication Abstract from PubMed

2'-5'-Oligoadenylate synthetases (OASs) produce the second messenger 2'-5'-oligoadenylate, which activates RNase L to induce an intrinsic antiviral state. We report on the crystal structures of catalytic intermediates of OAS1 including the OAS1.dsRNA complex without substrates, with a donor substrate, and with both donor and acceptor substrates. Combined with kinetic studies of point mutants and the previously published structure of the apo form of OAS1, the new data suggest a sequential mechanism of OAS activation and show the individual roles of each component. They reveal a dsRNA-mediated push-pull effect responsible for large conformational changes in OAS1, the catalytic role of the active site Mg(2+), and the structural basis for the 2'-specificity of product formation. Our data reveal similarities and differences in the activation mechanisms of members of the OAS/cyclic GMP-AMP synthase family of innate immune sensors. In particular, they show how helix 3103-alpha5 blocks the synthesis of cyclic dinucleotides by OAS1.

The Activation Mechanism of 2'-5'-Oligoadenylate Synthetase Gives New Insights Into OAS/cGAS Triggers of Innate Immunity.,Lohofener J, Steinke N, Kay-Fedorov P, Baruch P, Nikulin A, Tishchenko S, Manstein DJ, Fedorov R Structure. 2015 May 5;23(5):851-62. doi: 10.1016/j.str.2015.03.012. Epub 2015 Apr, 16. PMID:25892109^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kristiansen H, Scherer CA, McVean M, Iadonato SP, Vends S, Thavachelvam K, Steffensen TB, Horan KA, Kuri T, Weber F, Paludan SR, Hartmann R. Extracellular 2'-5' oligoadenylate synthetase stimulates RNase L-independent antiviral activity: a novel mechanism of virus-induced innate immunity. J Virol. 2010 Nov;84(22):11898-904. doi: 10.1128/JVI.01003-10. Epub 2010 Sep 15. PMID:20844035 doi:http://dx.doi.org/10.1128/JVI.01003-10
↑ Lohofener J, Steinke N, Kay-Fedorov P, Baruch P, Nikulin A, Tishchenko S, Manstein DJ, Fedorov R. The Activation Mechanism of 2'-5'-Oligoadenylate Synthetase Gives New Insights Into OAS/cGAS Triggers of Innate Immunity. Structure. 2015 May 5;23(5):851-62. doi: 10.1016/j.str.2015.03.012. Epub 2015 Apr, 16. PMID:25892109 doi:http://dx.doi.org/10.1016/j.str.2015.03.012

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4rwn"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the pre-reactive state of porcine OAS1==
-<StructureSection load='4rwn' size='340' side='right' caption='[[4rwn]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='4rwn' size='340' side='right'caption='[[4rwn]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4rwn]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RWN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RWN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4rwn]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Pig Pig]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RWN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RWN FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4rwq|4rwq]], [[4rwo|4rwo]], [[4rwp|4rwp]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">OAS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 PIG])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/2'-5'_oligoadenylate_synthase 2'-5' oligoadenylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.84 2.7.7.84] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rwn OCA], [http://pdbe.org/4rwn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rwn RCSB], [http://www.ebi.ac.uk/pdbsum/4rwn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rwn ProSAT]</span></td></tr>
@@ Line 25: / Line 26: @@
 </StructureSection>
 [[Category: 2'-5' oligoadenylate synthase]]
+[[Category: Large Structures]]
+[[Category: Pig]]
 [[Category: Baruch, P]]
 [[Category: Fedorov, R]]

4rwn

From Proteopedia

Revision as of 09:51, 1 May 2019

Crystal structure of the pre-reactive state of porcine OAS1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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