Sandbox Reserved 1685: Difference between revisions

Line 12:

==Conservation of RDRP Hand Structure==

Currently, there are two proposed drug candidates, verified through crystal structure, for Dengue serotype DEN-3; the two proposed small molecules for inhibition of Dengue RDRP are NITD-640 and <scene name='89/891375/6xd0_nitd-434_inhibition/1'>NITD-434</scene>. The finger subdomain in Dengue RDRP is made up of <scene name='89/891375/6j00_fingertip_domain/1'>residues 273-315, 416-496, and 543-600</scene>. The "fingertip region" has been shown to be more mobile than the palm and thumb subdomains. Consistent with other viral RDRPs there is an extended fingertip region in Dengue RDRP. Helix-6,14 and 15 are shaped by solvent-exposed residues which lead to the formation of a concave surface at the finger base. Unlike other RDRPs, however, there is an N-terminal segment of 35 amino acids added which is composed of helix-1 and strand-1 which connect to helix-two of NLS which is buried in the thumb domain. Two loop regions

Currently, there are two proposed drug candidates, verified through crystal structure, for Dengue serotype DEN-3; the two proposed small molecules for inhibition of Dengue RDRP are NITD-640 and <scene name='89/891375/6xd0_nitd-434_inhibition/1'>NITD-434</scene>. The finger subdomain in Dengue RDRP is made up of <scene name='89/891375/6j00_fingertip_domain/3'>residues 273-315, 416-496, and 543-600</scene>. The "fingertip region" has been shown to be more mobile than the palm and thumb subdomains. Consistent with other viral RDRPs there is an extended fingertip region in Dengue RDRP. Helix-6,14 and 15 are shaped by solvent-exposed residues which lead to the formation of a concave surface at the finger base. Unlike other RDRPs, however, there is an N-terminal segment of 35 amino acids added which is composed of helix-1 and strand-1 which connect to helix-two of NLS which is buried in the thumb domain. Two loop regions

<scene name='89/891375/6j00_fingertipthumb_domain/1'>(residues 309-321 and 342-347)</scene> link the finger and thumb domains. This linkage likely leads to confirmation changes between the two domains, thus hindering independent movement between these regions. In other RDRPs the fingertips of loops twist away from the active site, but in Dengue RDRP loop 3 regulates access of ssRNA substrate at the entrance of the template tunnel. The overall sequence conservation of the finger region of Dengue finger regions is quite low compared to other viral RDRPs.

Sandbox Reserved 1685: Difference between revisions

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 12: / Line 12: @@
 ==Conservation of RDRP Hand Structure==
-Currently, there are two proposed drug candidates, verified through crystal structure, for Dengue serotype DEN-3; the two proposed small molecules for inhibition of Dengue RDRP are NITD-640 and <scene name='89/891375/6xd0_nitd-434_inhibition/1'>NITD-434</scene>. The finger subdomain in Dengue RDRP is made up of <scene name='89/891375/6j00_fingertip_domain/1'>residues 273-315, 416-496, and 543-600</scene>. The "fingertip region" has been shown to be more mobile than the palm and thumb subdomains. Consistent with other viral RDRPs there is an extended fingertip region in Dengue RDRP. Helix-6,14 and 15 are shaped by solvent-exposed residues which lead to the formation of a concave surface at the finger base. Unlike other RDRPs, however, there is an N-terminal segment of 35 amino acids added which is composed of helix-1 and strand-1 which connect to helix-two of NLS which is buried in the thumb domain. Two loop regions
+Currently, there are two proposed drug candidates, verified through crystal structure, for Dengue serotype DEN-3; the two proposed small molecules for inhibition of Dengue RDRP are NITD-640 and <scene name='89/891375/6xd0_nitd-434_inhibition/1'>NITD-434</scene>. The finger subdomain in Dengue RDRP is made up of <scene name='89/891375/6j00_fingertip_domain/3'>residues 273-315, 416-496, and 543-600</scene>. The "fingertip region" has been shown to be more mobile than the palm and thumb subdomains. Consistent with other viral RDRPs there is an extended fingertip region in Dengue RDRP. Helix-6,14 and 15 are shaped by solvent-exposed residues which lead to the formation of a concave surface at the finger base. Unlike other RDRPs, however, there is an N-terminal segment of 35 amino acids added which is composed of helix-1 and strand-1 which connect to helix-two of NLS which is buried in the thumb domain. Two loop regions
 <scene name='89/891375/6j00_fingertipthumb_domain/1'>(residues 309-321 and 342-347)</scene> link the finger and thumb domains. This linkage likely leads to confirmation changes between the two domains, thus hindering independent movement between these regions. In other RDRPs the fingertips of loops twist away from the active site, but in Dengue RDRP loop 3 regulates access of ssRNA substrate at the entrance of the template tunnel. The overall sequence conservation of the finger region of Dengue finger regions is quite low compared to other viral RDRPs.