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2p1d
From Proteopedia
(New page: 200px<br /><applet load="2p1d" size="350" color="white" frame="true" align="right" spinBox="true" caption="2p1d, resolution 2.90Å" /> '''Crystal structure of...) |
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==Overview== | ==Overview== | ||
| - | Viruses represent an attractive system with which to study the molecular | + | Viruses represent an attractive system with which to study the molecular basis of mRNA capping and its relation to the RNA transcription machinery. The RNA-dependent RNA polymerase NS5 of flaviviruses presents a characteristic motif of S-adenosyl-L-methionine-dependent methyltransferases at its N-terminus, and polymerase motifs at its C-terminus. The crystal structure of an N-terminal fragment of Dengue virus type 2 NS5 is reported at 2.4 A resolution. We show that this NS5 domain includes a typical methyltransferase core and exhibits a (nucleoside-2'-O-)-methyltransferase activity on capped RNA. The structure of a ternary complex comprising S-adenosyl-L-homocysteine and a guanosine triphosphate (GTP) analogue shows that 54 amino acids N-terminal to the core provide a novel GTP-binding site that selects guanine using a previously unreported mechanism. Binding studies using GTP- and RNA cap-analogues, as well as the spatial arrangement of the methyltransferase active site relative to the GTP-binding site, suggest that the latter is a specific cap-binding site. As RNA capping is an essential viral function, these results provide a structural basis for the rational design of drugs against the emerging flaviviruses. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Benarooch, D.]] | [[Category: Benarooch, D.]] | ||
| - | [[Category: Egloff, M | + | [[Category: Egloff, M P.]] |
| - | [[Category: MSGP, Marseilles | + | [[Category: MSGP, Marseilles Structural Genomics Program.@.AFMB.]] |
[[Category: 5GP]] | [[Category: 5GP]] | ||
[[Category: SAH]] | [[Category: SAH]] | ||
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[[Category: vizier; viral enzymes involved in replication; dengue virus methyltransferase; structural genomics; marseilles structural genomics program @ afmb; msgp]] | [[Category: vizier; viral enzymes involved in replication; dengue virus methyltransferase; structural genomics; marseilles structural genomics program @ afmb; msgp]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:24:45 2008'' |
Revision as of 16:24, 21 February 2008
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Crystal structure of dengue methyltransferase in complex with GTP and S-Adenosyl-L-homocysteine
Overview
Viruses represent an attractive system with which to study the molecular basis of mRNA capping and its relation to the RNA transcription machinery. The RNA-dependent RNA polymerase NS5 of flaviviruses presents a characteristic motif of S-adenosyl-L-methionine-dependent methyltransferases at its N-terminus, and polymerase motifs at its C-terminus. The crystal structure of an N-terminal fragment of Dengue virus type 2 NS5 is reported at 2.4 A resolution. We show that this NS5 domain includes a typical methyltransferase core and exhibits a (nucleoside-2'-O-)-methyltransferase activity on capped RNA. The structure of a ternary complex comprising S-adenosyl-L-homocysteine and a guanosine triphosphate (GTP) analogue shows that 54 amino acids N-terminal to the core provide a novel GTP-binding site that selects guanine using a previously unreported mechanism. Binding studies using GTP- and RNA cap-analogues, as well as the spatial arrangement of the methyltransferase active site relative to the GTP-binding site, suggest that the latter is a specific cap-binding site. As RNA capping is an essential viral function, these results provide a structural basis for the rational design of drugs against the emerging flaviviruses.
About this Structure
2P1D is a Single protein structure of sequence from Dengue virus type 3 with , and as ligands. Active as RNA-directed RNA polymerase, with EC number 2.7.7.48 Full crystallographic information is available from OCA.
Reference
An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization., Egloff MP, Benarroch D, Selisko B, Romette JL, Canard B, EMBO J. 2002 Jun 3;21(11):2757-68. PMID:12032088
Page seeded by OCA on Thu Feb 21 18:24:45 2008
Categories: Dengue virus type 3 | RNA-directed RNA polymerase | Single protein | Benarooch, D. | Egloff, M P. | MSGP, Marseilles Structural Genomics Program.@.AFMB. | 5GP | SAH | SO4 | Vizier. viral enzymes involved in replication | Vizier; viral enzymes involved in replication; dengue virus methyltransferase; structural genomics; marseilles structural genomics program @ afmb; msgp
