PDBsum entry 2fp7

Hydrolase/hydrolase inhibitor

PDB id: 2fp7

Contents

Protein chains

40 a.a. *

147 a.a. *

Ligands

BEZ-NLE-LYS-ARG-OAR

Waters ×133

* Residue conservation analysis

PDB id:

2fp7

Name:

Hydrolase/hydrolase inhibitor

Title:

West nile virus ns2b/ns3protease in complex with bz-nle-lys-arg-arg-h

Structure:

Genome polyprotein. Chain: a. Fragment: ns2b. Ec: 3.4.21.91,3.6.1.15,3.6.4.13,2.1.1.56,2.1.1.57,2.7.7.48. Engineered: yes. Genome polyprotein. Chain: b. Fragment: ns3pro. Ec: 3.4.21.91,3.6.1.15,3.6.4.13,2.1.1.56,2.1.1.57,2.7.7.48.

Source:

West nile virus. Wnv. Organism_taxid: 11082. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Synthetic construct. Organism_taxid: 32630

Biol. unit:

Dimer (from PQS)

Resolution:

1.68Å R-factor: 0.182 R-free: 0.219

Authors:

N.Schiering,A.D'Arcy,P.Erbel

Key ref:

P.Erbel et al. (2006). Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus. Nat Struct Mol Biol, 13, 372-373. PubMed id: 16532006 DOI: 10.1038/nsmb1073

Date:

16-Jan-06 Release date: 07-Mar-06

Protein chain

P06935  (POLG_WNV) -  Genome polyprotein from West Nile virus

Seq: 3430 a.a.

Struc: 40 a.a.*

Protein chain

P06935  (POLG_WNV) -  Genome polyprotein from West Nile virus

Seq: 3430 a.a.

Struc: 147 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: Chains A, B: E.C.2.1.1.56 - mRNA (guanine-N(7))-methyltransferase.
• Reaction: a 5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L- methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-homocysteine
• Enzyme class 2: Chains A, B: E.C.2.1.1.57 - methyltransferase cap1.
• Reaction: a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)- (2'-O-methyl-ribonucleoside) in mRNA + S-adenosyl-L-homocysteine + H⁺
• Enzyme class 3: Chains A, B: E.C.2.7.7.48 - RNA-directed Rna polymerase.
• Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate
• Enzyme class 4: Chains A, B: E.C.3.4.21.91 - flavivirin.
• Reaction: Selective hydrolysis of Xaa-Xaa-|-Xbb bonds in which each of the Xaa can be either Arg or Lys and Xbb can be either Ser or Ala.
• Enzyme class 5: Chains A, B: E.C.3.6.1.15 - nucleoside-triphosphate phosphatase.
• Reaction: a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H⁺
• Enzyme class 6: Chains A, B: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + 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

reference

DOI no: 10.1038/nsmb1073

Nat Struct Mol Biol 13:372-373 (2006)

PubMed id: 16532006

Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus.

P.Erbel, N.Schiering, A.D'Arcy, M.Renatus, M.Kroemer, S.P.Lim, Z.Yin, T.H.Keller, S.G.Vasudevan, U.Hommel.

ABSTRACT

The replication of flaviviruses requires the correct processing of their polyprotein by the viral NS3 protease (NS3pro). Essential for the activation of NS3pro is a 47-residue region of NS2B. Here we report the crystal structures of a dengue NS2B-NS3pro complex and a West Nile virus NS2B-NS3pro complex with a substrate-based inhibitor. These structures identify key residues for NS3pro substrate recognition and clarify the mechanism of NS3pro activation.

Selected figure(s)

Figure 1.
Figure 1. Structures of NS2B–NS3pro in the absence and presence of an inhibitor. (a) DEN NS2B–NS3pro. Gray, NS3pro; yellow, NS2B. No electron density was observed for NS2B residues 77–84. (b) WNV NS2B–NS3pro in complex with Bz-Nle-Lys-Arg-Arg-H (orange). Residue numbering is according to Supplementary Figure 2. Figures were made in PyMOL (http://pymol.sourceforge.net/).

Figure 2.
Figure 2. Stereo view of the substrate-binding region of WNV NS2B–NS3pro, colored as in Figure 1. Potential hydrogen bonds are indicated (dotted lines).

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2006, 13, 372-373) copyright 2006.