PDBsum entry 1sh2

Transferase

PDB id

1sh2

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Contents

			Protein chain

					502 a.a. *

			Waters ×139

* Residue conservation analysis

PDB id:

1sh2

Links

Name:

Transferase

Title:

Crystal structure of norwalk virus polymerase (metal-free, centered orthorhombic)

Structure:

RNA polymerase. Chain: a. Fragment: c-terminus. Engineered: yes

Source:

Norwalk virus. Organism_taxid: 11983. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.30Å

R-factor:

0.231

R-free:

0.291

Authors:

K.K.Ng,N.Pendas-Franco,J.Rojo,J.A.Boga,A.Machin,J.M.Alonso,F.Parra

Key ref:

K.K.Ng et al. (2004). Crystal structure of norwalk virus polymerase reveals the carboxyl terminus in the active site cleft. J Biol Chem, 279, 16638-16645. PubMed id: 14764591 DOI: 10.1074/jbc.M400584200

Date:

24-Feb-04

Release date:

09-Mar-04

PROCHECK

	Headers

	References

Protein chain

Q70ET3 (Q70ET3_9CALI) - Genome polyprotein (Fragment) from Norwalk virus

Seq: Struc:

Seq: Struc:					838 a.a. 502 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class 1:

E.C.3.4.22.66 - calicivirin.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Enzyme class 2:

E.C.3.6.1.15 - nucleoside-triphosphate phosphatase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H⁺

ribonucleoside 5'-triphosphate	+	H2O	=	ribonucleoside 5'-diphosphate	+	phosphate	+	H(+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

DOI no: 10.1074/jbc.M400584200	J Biol Chem 279:16638-16645 (2004)
PubMed id: 14764591

Crystal structure of norwalk virus polymerase reveals the carboxyl terminus in the active site cleft.
K.K.Ng, N.Pendás-Franco, J.Rojo, J.A.Boga, A.Machín, J.M.Alonso, F.Parra.

ABSTRACT

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.

Selected figure(s)



	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.		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.

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20960046

R.A.Bull, J.Hyde, J.M.Mackenzie, G.S.Hansman, T.Oka, N.Takeda, and P.A.White (2011).
Comparison of the replication properties of murine and human calicivirus RNA-dependent RNA polymerases.

Virus Genes, 42, 16-27.

20219896

K.R.Han, Y.Choi, B.S.Min, H.Jeong, D.Cheon, J.Kim, Y.Jee, S.Shin, and J.M.Yang (2010).
Murine norovirus-1 3Dpol exhibits RNA-dependent RNA polymerase activity and nucleotidylylates on Tyr of the VPg.

J Gen Virol, 91, 1713-1722.

20534858

S.E.Hobdey, B.J.Kempf, B.P.Steil, D.J.Barton, and O.B.Peersen (2010).
Poliovirus polymerase residue 5 plays a critical role in elongation complex stability.

J Virol, 84, 8072-8084.

19141436

M.Högbom, K.Jäger, I.Robel, T.Unge, and J.Rohayem (2009).
The active form of the norovirus RNA-dependent RNA polymerase is a homodimer with cooperative activity.

J Gen Virol, 90, 281-291.

18234264

G.Belliot, S.V.Sosnovtsev, K.O.Chang, P.McPhie, and K.Y.Green (2008).
Nucleotidylylation of the VPg protein of a human norovirus by its proteinase-polymerase precursor protein.

Virology, 374, 33-49.

18268843

K.K.Ng, J.J.Arnold, and C.E.Cameron (2008).
Structure-function relationships among RNA-dependent RNA polymerases.

Curr Top Microbiol Immunol, 320, 137-156.

18667512

M.Hass, M.Lelke, C.Busch, B.Becker-Ziaja, and S.Günther (2008).
Mutational evidence for a structural model of the Lassa virus RNA polymerase domain and identification of two residues, Gly1394 and Asp1395, that are critical for transcription but not replication of the genome.

J Virol, 82, 10207-10217.

18940872

M.M.Poranen, P.S.Salgado, M.R.Koivunen, S.Wright, D.H.Bamford, D.I.Stuart, and J.M.Grimes (2008).
Structural explanation for the role of Mn2+ in the activity of phi6 RNA-dependent RNA polymerase.

Nucleic Acids Res, 36, 6633-6644.

PDB codes:

2jl9 2jlf 2jlg

17223130

A.A.Thompson, R.A.Albertini, and O.B.Peersen (2007).
Stabilization of poliovirus polymerase by NTP binding and fingers-thumb interactions.

J Mol Biol, 366, 1459-1474.

PDB codes:

2ily 2ilz 2im0 2im1 2im2 2im3

18077388

D.Garriga, A.Navarro, J.Querol-Audí, F.Abaitua, J.F.Rodríguez, and N.Verdaguer (2007).
Activation mechanism of a noncanonical RNA-dependent RNA polymerase.

Proc Natl Acad Sci U S A, 104, 20540-20545.

PDB codes:

2pus 2qj1 2r70 2r72

17456597

J.Pan, V.N.Vakharia, and Y.J.Tao (2007).
The structure of a birnavirus polymerase reveals a distinct active site topology.

Proc Natl Acad Sci U S A, 104, 7385-7390.

PDB code:

2pgg

17537850

N.Beerens, B.Selisko, S.Ricagno, I.Imbert, L.van der Zanden, E.J.Snijder, and B.Canard (2007).
De novo initiation of RNA synthesis by the arterivirus RNA-dependent RNA polymerase.

J Virol, 81, 8384-8395.

17121797

S.W.Fullerton, M.Blaschke, B.Coutard, J.Gebhardt, A.Gorbalenya, B.Canard, P.A.Tucker, and J.Rohayem (2007).
Structural and functional characterization of sapovirus RNA-dependent RNA polymerase.

J Virol, 81, 1858-1871.

PDB code:

2ckw

17301146

T.L.Yap, T.Xu, Y.L.Chen, H.Malet, M.P.Egloff, B.Canard, S.G.Vasudevan, and J.Lescar (2007).
Crystal structure of the dengue virus RNA-dependent RNA polymerase catalytic domain at 1.85-angstrom resolution.

J Virol, 81, 4753-4765.

PDB codes:

2j7u 2j7w

16641296

C.E.Zeitler, M.K.Estes, and B.V.Venkataram Prasad (2006).
X-ray crystallographic structure of the Norwalk virus protease at 1.5-A resolution.

J Virol, 80, 5050-5058.

PDB codes:

2fyq 2fyr

16719717

J.Ortín, and F.Parra (2006).
Structure and function of RNA replication.

Annu Rev Microbiol, 60, 305-326.

16843892

K.H.Choi, A.Gallei, P.Becher, and M.G.Rossmann (2006).
The structure of bovine viral diarrhea virus RNA-dependent RNA polymerase and its amino-terminal domain.

Structure, 14, 1107-1113.

PDB code:

2cjq

16940871

M.K.Estes, B.V.Prasad, and R.L.Atmar (2006).
Noroviruses everywhere: has something changed?

Curr Opin Infect Dis, 19, 467-474.

15681440

G.Belliot, S.V.Sosnovtsev, K.O.Chang, V.Babu, U.Uche, J.J.Arnold, C.E.Cameron, and K.Y.Green (2005).
Norovirus proteinase-polymerase and polymerase are both active forms of RNA-dependent RNA polymerase.

J Virol, 79, 2393-2403.

15878882

J.J.Arnold, M.Vignuzzi, J.K.Stone, R.Andino, and C.E.Cameron (2005).
Remote site control of an active site fidelity checkpoint in a viral RNA-dependent RNA polymerase.

J Biol Chem, 280, 25706-25716.

15901487

J.M.Martín-Alonso, D.E.Skilling, L.González-Molleda, G.del Barrio, A.Machín, N.K.Keefer, D.O.Matson, P.L.Iversen, A.W.Smith, and F.Parra (2005).
Isolation and characterization of a new Vesivirus from rabbits.

Virology, 337, 373-383.

16168575

M.E.Hardy (2005).
Norovirus protein structure and function.

FEMS Microbiol Lett, 253, 1-8.

15596823

T.C.Appleby, H.Luecke, J.H.Shim, J.Z.Wu, I.W.Cheney, W.Zhong, L.Vogeley, Z.Hong, and N.Yao (2005).
Crystal structure of complete rhinovirus RNA polymerase suggests front loading of protein primer.

J Virol, 79, 277-288.

PDB code:

1tp7

15306852

A.A.Thompson, and O.B.Peersen (2004).
Structural basis for proteolysis-dependent activation of the poliovirus RNA-dependent RNA polymerase.

EMBO J, 23, 3462-3471.

PDB codes:

1ra6 1ra7 1raj 1tql

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.