Sandbox Reserved 1088: Difference between revisions

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Dengue fever manifests as a combination of severe headache, chills, backache and joint pain. DHF is a potentially deadly form of the fever characterized by sudden increase in body temperature and impaired blood homeostasis and clotting. DSS involves further impairment due to blood loss. Dengue virus can inhibit various mediators of the innate immune system such as interferons and bypass the inflammatory response<ref name= "Mangold">PMID:23640151</ref>.

There are four serotypes of the virus (DENV-1 – DENV-4) whose respective genomes share 60% sequence identity, with 90% sequence identity within a serotype<ref name= "Yap"/>. The viral genome encodes three structural proteins (capsid, membrane and envelope) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). By associating with host co-factors and each other, NS proteins form multi-protein replication complexes, which comprise the viral replication machinery. ~~The~~ NS5 ~~primary sequence~~ is ~~generally well~~ conserved ~~across~~ serotypes and also shares some similarity with the NS5 protein of other flaviviruses<ref name= "Yap"/><ref name= "Wu"/>.

There are four serotypes of the virus (DENV-1 – DENV-4) whose respective genomes share 60% sequence identity, with 90% sequence identity within a serotype<ref name= "Yap"/>. The viral genome encodes three structural proteins (capsid, membrane and envelope) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). By associating with host co-factors and each other, NS proteins form multi-protein replication complexes, which comprise the viral replication machinery. NS5 is also the most conserved among the viral proteins with at least 67% sequence similarity among the four serotypes and also shares some similarity with the NS5 protein of other flaviviruses<ref name= "Yap">PMID:17301146</ref><ref name= "Wu"/>.

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[[Image:NS5.JPG|right|200px|thumb|Overall structure of DENV NS5 highlighting functional domains and key inter-domain interactions]]

NS5 is a 104 kDa, 900 amino acids long protein, making it the largest of the DENV proteins. ~~NS5 is also the most conserved among the viral proteins with at least 67% sequence similarity among the four serotypes<ref name= "Yap">PMID:17301146</ref>. According to~~ structural and biochemical studies, two functional domains exist within NS5. These being a S-adenosyl-L-methionine (SAM)-dependent methyltransferase (MTase) domain which spans residues 6-262 and a RNA-dependent RNA polymerase (RdRp) domain spanning residues 273-883 that are connected to each other by a flexible linker 10 amino acids in length (residues 263-272)<ref name= "Zhao"/>.

NS5 is a 104 kDa, 900 amino acids long protein, making it the largest of the DENV proteins. As per structural and biochemical studies, two functional domains exist within NS5. These being a S-adenosyl-L-methionine (SAM)-dependent methyltransferase (MTase) domain which spans residues 6-262 and a RNA-dependent RNA polymerase (RdRp) domain spanning residues 273-883 that are connected to each other by a flexible linker 10 amino acids in length (residues 263-272)<ref name= "Zhao"/>.

== Methyltransferase domain ==

Sandbox Reserved 1088: Difference between revisions

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@@ Line 13: / Line 13: @@
 Dengue fever manifests as a combination of severe headache, chills, backache and joint pain. DHF is a potentially deadly form of the fever characterized by sudden increase in body temperature and impaired blood homeostasis and clotting. DSS involves further impairment due to blood loss. Dengue virus can inhibit various mediators of the innate immune system such as interferons and bypass the inflammatory response<ref name= "Mangold">PMID:23640151</ref>.
-There are four serotypes of the virus (DENV-1 – DENV-4) whose respective genomes share 60% sequence identity, with 90% sequence identity within a serotype<ref name= "Yap"/>. The viral genome encodes three structural proteins (capsid, membrane and envelope) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). By associating with host co-factors and each other, NS proteins form multi-protein replication complexes, which comprise the viral replication machinery.  The NS5 primary sequence is generally well conserved across serotypes and also shares some similarity with the NS5 protein of other flaviviruses<ref name= "Yap"/><ref name= "Wu"/>.
+There are four serotypes of the virus (DENV-1 – DENV-4) whose respective genomes share 60% sequence identity, with 90% sequence identity within a serotype<ref name= "Yap"/>. The viral genome encodes three structural proteins (capsid, membrane and envelope) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). By associating with host co-factors and each other, NS proteins form multi-protein replication complexes, which comprise the viral replication machinery.  NS5 is also the most conserved among the viral proteins with at least 67% sequence similarity among the four serotypes and also shares some similarity with the NS5 protein of other flaviviruses<ref name= "Yap">PMID:17301146</ref><ref name= "Wu"/>.
@@ Line 22: / Line 22: @@
 [[Image:NS5.JPG|right|200px|thumb|Overall structure of DENV NS5 highlighting functional domains and key inter-domain interactions]]
-NS5 is a 104 kDa, 900 amino acids long protein, making it the largest of the DENV proteins. NS5 is also the most conserved among the viral proteins with at least 67% sequence similarity among the four serotypes<ref name= "Yap">PMID:17301146</ref>. According to structural and biochemical studies, two functional domains exist within NS5. These being a S-adenosyl-L-methionine (SAM)-dependent methyltransferase (MTase) domain which spans residues 6-262 and a RNA-dependent RNA polymerase (RdRp) domain spanning residues 273-883 that are connected to each other by a flexible linker 10 amino acids in length (residues 263-272)<ref name= "Zhao"/>.
+NS5 is a 104 kDa, 900 amino acids long protein, making it the largest of the DENV proteins. As per structural and biochemical studies, two functional domains exist within NS5. These being a S-adenosyl-L-methionine (SAM)-dependent methyltransferase (MTase) domain which spans residues 6-262 and a RNA-dependent RNA polymerase (RdRp) domain spanning residues 273-883 that are connected to each other by a flexible linker 10 amino acids in length (residues 263-272)<ref name= "Zhao"/>.
 == Methyltransferase domain ==