2bmf: Difference between revisions

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==Overview==

Dengue fever is an important emerging public health concern, with several, million viral infections occurring annually, for which no effective, therapy currently exists. The NS3 protein from Dengue virus is a, multifunctional protein of 69 kDa, endowed with protease, helicase, and, nucleoside 5'-triphosphatase (NTPase) activities. Thus, NS3 plays an, important role in viral replication and represents a very interesting, target for the development of specific antiviral inhibitors. We present, the structure of an enzymatically active fragment of the Dengue virus, NTPase/helicase catalytic domain to 2.4 A resolution. The structure is, composed of three domains, displays an asymmetric distribution of charges, on its surface, and contains a tunnel large enough to accommodate, single-stranded RNA. Its C-terminal domain adopts a new fold compared to, the NS3 helicase of hepatitis C virus, which has interesting implications, for the evolution of the Flaviviridae replication complex. A bound sulfate, ion reveals residues involved in the metal-dependent NTPase catalytic, mechanism. Comparison with the NS3 hepatitis C virus helicase complexed to, single-stranded DNA would place the 3' single-stranded tail of a nucleic, acid duplex in the tunnel that runs across the basic face of the protein., A possible model for the unwinding mechanism is proposed.

Dengue fever is an important emerging public health concern, with several million viral infections occurring annually, for which no effective therapy currently exists. The NS3 protein from Dengue virus is a multifunctional protein of 69 kDa, endowed with protease, helicase, and nucleoside 5'-triphosphatase (NTPase) activities. Thus, NS3 plays an important role in viral replication and represents a very interesting target for the development of specific antiviral inhibitors. We present the structure of an enzymatically active fragment of the Dengue virus NTPase/helicase catalytic domain to 2.4 A resolution. The structure is composed of three domains, displays an asymmetric distribution of charges on its surface, and contains a tunnel large enough to accommodate single-stranded RNA. Its C-terminal domain adopts a new fold compared to the NS3 helicase of hepatitis C virus, which has interesting implications for the evolution of the Flaviviridae replication complex. A bound sulfate ion reveals residues involved in the metal-dependent NTPase catalytic mechanism. Comparison with the NS3 hepatitis C virus helicase complexed to single-stranded DNA would place the 3' single-stranded tail of a nucleic acid duplex in the tunnel that runs across the basic face of the protein. A possible model for the unwinding mechanism is proposed.

==About this Structure==

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[[Category: Nanao, M.]]

[[Category: Sampath, A.]]

[[Category: Vasudevan, S.G.]]

[[Category: Vasudevan, S G.]]

[[Category: Wen, D.]]

[[Category: Xu, T.]]

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[[Category: rna helicase]]

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@@ Line 4: / Line 4: @@
 ==Overview==
-Dengue fever is an important emerging public health concern, with several, million viral infections occurring annually, for which no effective, therapy currently exists. The NS3 protein from Dengue virus is a, multifunctional protein of 69 kDa, endowed with protease, helicase, and, nucleoside 5'-triphosphatase (NTPase) activities. Thus, NS3 plays an, important role in viral replication and represents a very interesting, target for the development of specific antiviral inhibitors. We present, the structure of an enzymatically active fragment of the Dengue virus, NTPase/helicase catalytic domain to 2.4 A resolution. The structure is, composed of three domains, displays an asymmetric distribution of charges, on its surface, and contains a tunnel large enough to accommodate, single-stranded RNA. Its C-terminal domain adopts a new fold compared to, the NS3 helicase of hepatitis C virus, which has interesting implications, for the evolution of the Flaviviridae replication complex. A bound sulfate, ion reveals residues involved in the metal-dependent NTPase catalytic, mechanism. Comparison with the NS3 hepatitis C virus helicase complexed to, single-stranded DNA would place the 3' single-stranded tail of a nucleic, acid duplex in the tunnel that runs across the basic face of the protein., A possible model for the unwinding mechanism is proposed.
+Dengue fever is an important emerging public health concern, with several million viral infections occurring annually, for which no effective therapy currently exists. The NS3 protein from Dengue virus is a multifunctional protein of 69 kDa, endowed with protease, helicase, and nucleoside 5'-triphosphatase (NTPase) activities. Thus, NS3 plays an important role in viral replication and represents a very interesting target for the development of specific antiviral inhibitors. We present the structure of an enzymatically active fragment of the Dengue virus NTPase/helicase catalytic domain to 2.4 A resolution. The structure is composed of three domains, displays an asymmetric distribution of charges on its surface, and contains a tunnel large enough to accommodate single-stranded RNA. Its C-terminal domain adopts a new fold compared to the NS3 helicase of hepatitis C virus, which has interesting implications for the evolution of the Flaviviridae replication complex. A bound sulfate ion reveals residues involved in the metal-dependent NTPase catalytic mechanism. Comparison with the NS3 hepatitis C virus helicase complexed to single-stranded DNA would place the 3' single-stranded tail of a nucleic acid duplex in the tunnel that runs across the basic face of the protein. A possible model for the unwinding mechanism is proposed.
 ==About this Structure==
@@ Line 18: / Line 18: @@
 [[Category: Nanao, M.]]
 [[Category: Sampath, A.]]
-[[Category: Vasudevan, S.G.]]
+[[Category: Vasudevan, S G.]]
 [[Category: Wen, D.]]
 [[Category: Xu, T.]]
@@ Line 25: / Line 25: @@
 [[Category: rna helicase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 18:27:13 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:39:23 2008''