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PDBsum entry 1sh2
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of norwalk virus polymerase reveals the carboxyl terminus in the active site cleft.
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Authors
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K.K.Ng,
N.Pendás-Franco,
J.Rojo,
J.A.Boga,
A.Machín,
J.M.Alonso,
F.Parra.
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Ref.
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J Biol Chem, 2004,
279,
16638-16645.
[DOI no: ]
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PubMed id
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Abstract
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Norwalk virus is a major cause of acute gastroenteritis for which effective
treatments are sorely lacking. To provide a basis for the rational design of
novel antiviral agents, the main replication enzyme in Norwalk virus, the
virally encoded RNA-dependent RNA polymerase (RdRP), has been expressed in an
enzymatically active form, and its structure has been crystallographically
determined both in the presence and absence of divalent metal cations. Although
the overall fold of the enzyme is similar to that seen previously in the RdRP
from rabbit hemorrhagic disease virus, the carboxyl terminus, surprisingly, is
located in the active site cleft in five independent copies of the protein in
three distinct crystal forms. The location of this carboxyl-terminal segment
appears to interfere with the binding of double-stranded RNA in the active site
cleft and may play a role in the initiation of RNA synthesis or mediate
interactions with accessory replication proteins.
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Figure 2.
FIG. 2. A, carboxyl-terminal segment of NV RdRP LIGPLOT
(22) diagram of hydrogen bonding (dashed green lines) and van
der Waals interactions between residues 501-507 and other
residues in the polymerase. B, stereoview of a sigma-A-weighted
2|F[o]| -|F[c]| electron density map (contoured at 1  ) in the
region of the carboxyl-terminal segment and adjacent regions.
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Figure 4.
FIG. 4. Model of metal ion, NTP and RNA binding to NV RdRP
constructed by comparison with the structure of the human
immunodeficiency virus-1 reverse
transcriptase·TTP·DNA ternary complex (52).
"Front" (A) and "top" (B) stereoviews of the modeled complex.
The carboxyl-terminal segment (residues 503-507) is drawn as a
space-filling and ball-and-stick representation, respectively,
in the two panels.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2004,
279,
16638-16645)
copyright 2004.
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