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PDBsum entry 4o1o
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Transferase,hydrolase
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PDB id
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4o1o
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PDB id:
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| Name: |
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Transferase,hydrolase
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Title:
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Crystal structure of rnase l in complex with 2-5a
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Structure:
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Ribonuclease l. Chain: a, b, c, d. Fragment: unp residues 21-732. Engineered: yes
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Source:
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Sus scrofa. Pigs,swine,wild boar. Organism_taxid: 9823. Gene: rnasel. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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3.27Å
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R-factor:
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0.232
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R-free:
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0.289
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Authors:
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H.Huang,E.Zeqiraj,D.F.Ceccarelli,F.Sicheri
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Key ref:
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H.Huang
et al.
(2014).
Dimeric structure of pseudokinase RNase L bound to 2-5A reveals a basis for interferon-induced antiviral activity.
Mol Cell,
53,
221-234.
PubMed id:
DOI:
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Date:
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16-Dec-13
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Release date:
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05-Feb-14
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PROCHECK
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Headers
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References
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A5H025
(A5H025_PIG) -
Ribonuclease L from Sus scrofa
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Seq:
Struc:
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743 a.a.
672 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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DOI no:
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Mol Cell
53:221-234
(2014)
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PubMed id:
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Dimeric structure of pseudokinase RNase L bound to 2-5A reveals a basis for interferon-induced antiviral activity.
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H.Huang,
E.Zeqiraj,
B.Dong,
B.K.Jha,
N.M.Duffy,
S.Orlicky,
N.Thevakumaran,
M.Talukdar,
M.C.Pillon,
D.F.Ceccarelli,
L.C.Wan,
Y.C.Juang,
D.Y.Mao,
C.Gaughan,
M.A.Brinton,
A.A.Perelygin,
I.Kourinov,
A.Guarné,
R.H.Silverman,
F.Sicheri.
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ABSTRACT
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RNase L is an ankyrin repeat domain-containing dual
endoribonuclease-pseudokinase that is activated by unusual 2,'5'-oligoadenylate
(2-5A) second messengers and which impedes viral infections in higher
vertebrates. Despite its importance in interferon-regulated antiviral innate
immunity, relatively little is known about its precise mechanism of action. Here
we present a functional characterization of 2.5 Å and 3.25 Å X-ray crystal and
small-angle X-ray scattering structures of RNase L bound to a natural 2-5A
activator with and without ADP or the nonhydrolysable ATP mimetic AMP-PNP. These
studies reveal how recognition of 2-5A through interactions with the ankyrin
repeat domain and the pseudokinase domain, together with nucleotide binding,
imposes a rigid intertwined dimer configuration that is essential for RNase
catalytic and antiviral functions. The involvement of the pseudokinase domain of
RNase L in 2-5A sensing, nucleotide binding, dimerization, and ribonuclease
functions highlights the evolutionary adaptability of the eukaryotic protein
kinase fold.
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