https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Sunjeet+VirdiProteopedia - User contributions [en]2026-09-29T21:49:06ZUser contributionsMediaWiki 1.43.8https://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1867234Sandbox 1k4r2013-11-22T04:52:59Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus (1-4). Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
'''Dengue Virus Genome''' carries only one single strand of RNA as its genome. This genome only encodes for ten proteins (three structural and seven "production" proteins). The production proteins are useful in aiding the virus to penetrate the host cell and help produce new virus structures. The outer membrane of the protein is constructed of 180 copies of the envelope protein, which this membrane helps the virus attach to the host cell membrane. <br />
<br />
[[Image:1ok8 copy.jpg]]'''Figure 1:''' ''This image represents the entire Dengue genome (complete with 180 copies of the envelope protein)''<br />
<br />
<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''><br />
'''Dengue Virus inside Cell''' ([[1ok8]])<br />
When the virus is in its infectious form the surface is smooth (''figure 1''), but as it is exposed to the acidic environment of the cell cytoplasm, this causes the proteins to snap into a trimeric spike (or trimer), which allows it to penetrate and fuse with the lysozome membrane of the host cell.<br />
In experimental laboratory settings, the extraction or isolation of this trimer model can be done in many different ways. The main, observed, extraction was separated by detergent isolation. The model shows a chloride ion (detergent) liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or <scene name='56/565763/Trimer/3'>fusion loop</scene>, displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. <br />
Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108<br />
</StructureSection><br />
<br />
<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''><br />
'''Dengue NS5 Protein''' ([[2j7w]])<br />
The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase (which helps replicate its RNA). The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus (1-4), and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine (SAM) ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. The SAM and SAH are useful in aiding in the folding of the active site.<br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <br />
<scene name='56/565763/Active_site_gtp/4'>GTP in the binding site</scene> is what allows the Dengue-2-methyltransferase to complete its functions; these functions include translation, transcription and replication processes.</StructureSection> <br />
<br />
<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>'''Dengue NS3/NS2B Protein''' ([[2vbc]])<br />
The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two beta barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/7'>NS2B</scene> cofactor. This cofactor then wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that NS2B acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1867233Sandbox 1k4r2013-11-22T04:49:10Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
'''Dengue Virus Genome''' carries only one single strand of RNA as its genome. This genome only encodes for ten proteins (three structural and seven "production" proteins). The production proteins are useful in aiding the virus to penetrate the host cell and help produce new virus structures. The outer membrane of the protein is constructed of 180 copies of the envelope protein, which this membrane helps the virus attach to the host cell membrane. <br />
<br />
[[Image:1ok8 copy.jpg]]'''Figure 1:''' ''This image represents the entire Dengue genome (complete with 180 copies of the envelope protein)''<br />
<br />
<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''><br />
'''Dengue Virus inside Cell''' ([[1ok8]])<br />
When the virus is in its infectious form the surface is smooth (''figure 1''), but as it is exposed to the acidic environment of the cell cytoplasm, this causes the proteins to snap into a trimeric spike (or trimer), which allows it to penetrate and fuse with the lysozome membrane of the host cell.<br />
In experimental laboratory settings, the extraction or isolation of this trimer model can be done in many different ways. The main, observed, extraction was separated by detergent isolation. The model shows a chloride ion (detergent) liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or <scene name='56/565763/Trimer/3'>fusion loop</scene>, displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. <br />
Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108<br />
</StructureSection><br />
<br />
<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''><br />
'''Dengue NS5 Protein''' ([[2j7w]])<br />
The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine (SAM) ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. The SAM and SAH are useful in aiding in the folding of the active site.<br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <br />
<scene name='56/565763/Active_site_gtp/4'>GTP in the binding site</scene> is what allows the Dengue-2-methyltransferase to complete its functions; these functions include translation, transcription and replication processes.</StructureSection> <br />
<br />
<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>'''Dengue NS3/NS2B Protein''' ([[2vbc]])<br />
The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/7'>NS2B</scene>. This cofactor then wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that NS2B acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1867232Sandbox 1k4r2013-11-22T04:46:48Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
'''Dengue Virus Genome''' carries only one single strand of RNA as its genome. This genome only encodes for ten proteins (three structural and seven "production" proteins). The production proteins are useful in aiding the virus to penetrate the host cell and help produce new virus structures. The outer membrane of the protein is constructed of 180 copies of the envelope protein, which this membrane helps the virus attach to the host cell membrane. <br />
<br />
[[Image:1ok8 copy.jpg]]'''Figure 1:''' ''This image represents the entire Dengue genome (complete with 180 copies of the envelope protein)''<br />
<br />
<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''><br />
'''Dengue Virus inside Cell''' ([[1ok8]])<br />
When the virus is in its infectious form the surface is smooth (''figure 1''), but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike (or trimer, which allows it to penetrate and fuse with the lysozome membrane of the host cell.<br />
In experimental laboratory settings, the extraction of this trimer model can be done in many different ways. The main, observed, extraction was separated by detergent isolation. The model shows a chloride ion (detergent) liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or <scene name='56/565763/Trimer/3'>fusion loop</scene>, displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. <br />
Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108<br />
</StructureSection><br />
<br />
<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''><br />
'''Dengue NS5 Protein''' ([[2j7w]])<br />
The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine (SAM) ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. The SAM and SAH are useful in aiding in the folding of the active site.<br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <br />
<scene name='56/565763/Active_site_gtp/4'>GTP in the binding site</scene> is what allows the Dengue-2-methyltransferase to complete its functions; these functions include translation, transcription and replication processes.</StructureSection> <br />
<br />
<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>'''Dengue NS3/NS2B Protein''' ([[2vbc]])<br />
The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/7'>NS2B</scene>. This cofactor then wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that NS2B acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_vdr&diff=1867191Sandbox vdr2013-11-21T15:46:41Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Vitamin D Receptor ==<br />
<br />
{{STRUCTURE_1db1| PDB=1db1 | SCENE= }} <br />
<br />
'''Vitamin D receptor''' (<scene name='56/562378/Vit_d_receptor_3m7r/3'>VDR</scene>) is a transcription factor. Upon binding to vitamin D, VDR forms a heterodimer with retinoid-X receptor and binds to hormone response receptors on DNA causing gene expression. The <scene name='56/562378/Vit_d_receptor_ligand/1'>vitamin D hormone</scene> (in green) binds to receptors in its target cells, controlling the synthesis of many different proteins involved in calcium transport and utilization. VDR contains two domains: a <scene name='56/562378/Lbd/1'>ligand binding domain (LBD)</scene> that binds to the hormone and <scene name='56/562378/Dbd/2'>DNA-binding domain (DBD)</scene> that binds to DNA. It pairs up with a similar protein, 9-cis retinoic acid receptor (RXR), and together they bind to the DNA, activating synthesis in some cases and repressing it in others.<br />
<br />
===Crystal Structure of the nuclear receptor for Vitamnin D complexed to Vitamin D===<br />
<br />
{{ABSTRACT_PUBMED_10678179}}<br />
<br />
==Disease==<br />
[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[http://omim.org/entry/277440 277440]]. A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.<ref>PMID:2849209</ref><ref>PMID:8381803</ref><ref>PMID:1652893</ref><ref>PMID:2177843</ref><ref>PMID:8106618</ref><ref>PMID:8392085</ref><ref>PMID:7828346</ref><ref>PMID:8675579</ref><ref>PMID:8961271</ref><ref>PMID:9005998</ref> <br />
<br />
<br />
==Function==<br />
Vitamin D plays an essential role in regulating the levels of calcium and phosphate in the body. It is converted into a hormone that is secreted by the kidneys and travels through the body. It has major effects on intestinal cells, where it helps control the uptake of calcium, and bone cells, where it helps control the formation and maintenance of the skeleton.<br />
<br />
[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Nuclear hormone receptor: Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<ref>PMID:16252006</ref><ref>PMID:10678179</ref><ref>PMID:15728261</ref><ref>PMID:16913708</ref><br />
<br />
<br />
==Mutation==<br />
<StructureSection load='VDRmutation1.pdb' size='350' side='right' caption='Mutation of Vitamin D Receptor' scene=''>Amino acids like serine and threonine kinase plays a crucial role in signal transduction pathways drawn out by variety of growth factors, hormones, and neurotransmitters. When <scene name='56/562378/Serine_final/1'>serine</scene> is mutated it is replaced with a <scene name='56/562378/Glycine_final/1'>glycine</scene> which results in an inhibition of transcriptional activation. When transcription is inhibited it results in p53 accumulation, which activates and promotes p53 translocation into mitochondria leading to apoptosis. Transcription inhibition is useful in cancer patients and so can be used as treatment option. The research is still continuing for find the potential cure of cancer from this mutation. <br />
<br />
<br />
<br />
<scene name='56/562378/Serine_final/1'>Serine</scene> is replaced with <scene name='56/562378/Asparticacid_final/1'>aspartic acid</scene> when mutated creating a negative charge. The negative charge at the residue inhibits DNA binding which cause a down – regulation of VDR activity. VDR needs DNA binding in order for it to be activated which is only possible with a serine residue. Research is still continuing to find a therapeutic cause for this mutation. <br />
</StructureSection><br />
<br />
==Crystal structure of the human VDR ligand binding domain bound to the synthetic agonist compound 2alpha-methyl-AMCR277A(C23S)==<br />
<StructureSection load='3a3z' size='350' side='right' caption='Synthetic agonist (PDB entry [[3a3z]])' scene=''>Research showed that <scene name='56/562378/3a3z/1'>the synthetic analogue (20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (2a)</scene> acts as a 1alpha,25(OH)(2)D(3) superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1alpha,25(OH)(2)D(3), 2alpha-methyl-1alpha,25(OH)(2)D(3), or 2a, we designed a novel analogue, 2alpha-methyl-(20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes.<br />
</StructureSection> <br />
<br />
<br />
<br />
==About this Structure==<br />
[[1db1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DB1 OCA]. On right hand side is Structure of human vitamin D receptor ligand-binding domain complex with vitamin D (PDB entry [[1db1]]).<br />
<br />
<br />
==See Also==<br />
*[[Vitamin D receptor|Vitamin D receptor]]<br />
<br />
<br />
== 3D Structures of vitamin D receptor==<br />
<br />
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}<br />
<br />
===Vitamin D receptor ligand-binding domain===<br />
<br />
[[3m7r]] - hVDR LBD (mutant) – human<br /><br />
<br />
[[1db1]] – hVDR LBD + vitamin D <br /><br />
[[1s0z]], [[1s19]], [[3a78]], [[4g2i]] - hVDR LBD + vitamin D derivative<br /><br />
[[3ogt]], [[2ham]], [[2har]], [[2has]], [[2hb7]], [[2hb8]], [[3p8x]], [[3az1]], [[3az2]], [[3az3]], [[3tkc]] - hVDR LBD + vitamin D analog<br /><br />
[[3auq]], [[3aur]], [[3kpz]] - hVDR LBD (mutant) + vitamin D analog<br /><br />
[[3a2i]], [[3a2j]], [[3b0t]], [[3ax8]], [[3vhw]] - hVDR LBD (mutant) + vitamin D derivative<br /><br />
[[3a3z]], [[3a40]] - hVDR LBD + agonist<br /><br />
[[1ie8]], [[1ie9]], [[3cs4]], [[3cs6]], [[1txi]] – hVDR LBD + superagonist <br /><br />
[[3w5q]], [[3w5r]], [[3w5t]] - hVDR LBD + lithocholic acid derivative <br /><br />
<br />
''Vitamin D receptor LBD complex with peptide''<br />
<br />
[[1rjk]], [[1rk3]], [[1rkg]], [[1rkh]], [[2o4j]], [[2o4r]] – rVDR LBD (mutant) + peroxisome proliferator-activated receptor peptide – rat<br /><br />
[[2zl9]], [[2zla]], [[2zlc]] - rVDR LBD + coactivator peptide DRIP + vitamin D analog<br /><br />
[[3vrt]], [[3vru]], [[3vrv]], [[3vrw]] - rVDR LBD (mutant) + coactivator peptide DRIP + vitamin D analog<br /><br />
[[2zfx]], [[3a2h]], [[2zxm]], [[2zxn]] - rVDR LBD + coactivator peptide DRIP<br /><br />
[[3aun]], [[2zmh]], [[2zmi]], [[2zmj]], [[3afr]], [[3vjs]], [[3vjt]] - rVDR LBD (mutsant) + coactivator peptide DRIP<br /><br />
[[2hbh]] - zVDR LBD + steroid receptor coactivator 1 peptide – zebrafish<br /><br />
[[2hc4]] - zVDR LBD + steroid receptor coactivator 1 peptide + vitamin D<br /><br />
[[2hcd]] - zVDR LBD + steroid receptor coactivator 1 peptide <br />
<br />
===Vitamin D receptor DNA-binding domain===<br />
<br />
[[1kb2]] – hVDR DBD + osteopontin response element DNA<br /><br />
[[1kb4]] – hVDR DBD + DR3 response element DNA<br /><br />
[[1ynw]] – hVDR DBD (mutant) + DR3 response element DNA<br /><br />
[[1kb6]] – hVDR DBD + osteocalcin response element DNA<br /><br />
<br />
</StructureSection><br />
[[Category:Topic Page]]<br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:010678179</ref><ref group="xtra">PMID:011344298</ref><references group="xtra"/><references/><br />
[[Category: Homo sapiens]]<br />
[[Category: Klaholz, B.]]<br />
[[Category: Mitschler, A.]]<br />
[[Category: Moras, D.]]<br />
[[Category: Rochel, N.]]<br />
[[Category: Wurtz, J M.]]<br />
[[Category: Complex]]<br />
[[Category: Gene regulation]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1864550Sandbox 1k4r2013-11-14T16:42:17Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
'''Dengue Virus Genome''' carries only one single strand of RNA as its genome. This genome only encodes for ten proteins (three structural and seven "production" proteins. The production proteins are useful in aiding the virus penetrating the host cell and help produce new virus structures. The outer membrane of the protein is constructed of 180 copies of the envelope protein, which this membrane helps the virus attach to the host cell membrane. <br />
<br />
[[Image:1ok8 copy.jpg]]'''Figure 1:''' ''This image represents the entire Dengue genome (complete with 180 copies of the envelope protein)''<br />
<br />
<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''><br />
'''Dengue Virus inside Cell''' ([[1ok8]])<br />
When the virus is in its infectious form the surface is smooth (''figure 1''), but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike (or trimer, which allows it to penetrate and fuse with the lysozome membrane of the host cell.<br />
In experimental laboratory settings, the extraction of this trimer model can be done in many different ways. The main, observed, extraction was separated by detergent isolation. The model shows a chloride ion (detergent) liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or <scene name='56/565763/Trimer/3'>fusion loop</scene>, displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. <br />
Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108<br />
</StructureSection><br />
<br />
<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''><br />
'''Dengue NS5 Protein''' ([[2j7w]])<br />
The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine (SAM) ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. The SAM and SAH are useful in aiding in the folding of the active site.<br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <br />
<scene name='56/565763/Active_site_gtp/4'>GTP in the binding site</scene> is what allows the Dengue-2-methyltransferase to complete its functions; these functions include translation, transcription and replication processes.</StructureSection> <br />
<br />
<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>'''Dengue NS3/NS2B Protein''' ([[2vbc]])<br />
The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/7'>NS2B</scene>. This cofactor then wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that NS2B acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1864545Sandbox 1k4r2013-11-14T16:31:54Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
'''Dengue Virus Genome''' carries only one single strand of RNA as its genome. This genome only encodes for ten proteins (three structural and seven "production" proteins. The production proteins are useful in aiding the virus penetrating the host cell and help produce new virus structures. The outer membrane of the protein is constructed of 180 copies of the envelope protein, which this membrane helps the virus attach to the host cell membrane. <br />
<br />
[[Image:1ok8 copy.jpg]]'''Figure 1:''' ''This image represents the entire Dengue genome (complete with 180 copies of the envelope protein)''<br />
<br />
<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''><br />
'''Dengue Virus inside Cell'''[[1ok8]]<br />
When the virus is in its infectious form the surface is smooth (''figure 1''), but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike (or trimer, which allows it to penetrate and fuse with the lysozome membrane of the host cell.<br />
The trimer model of the Dengue virus is extracted in many different ways. The one observed extraction was separated by detergent isolation. The model shows a chloride ion (detergent) liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or <scene name='56/565763/Trimer/3'>fusion loop</scene>, displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. <br />
Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108<br />
</StructureSection><br />
<br />
<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''><br />
'''Dengue NS5 Protein'''[[2j7w]]<br />
The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine (SAM) ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. The SAM and SAH are useful in aiding in the folding of the active site.<br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <br />
<scene name='56/565763/Active_site_gtp/4'>GTP in the binding site</scene> is what allows the Dengue-2-methyltransferase to complete its functions; these functions include translation, transcription and replication processes.</StructureSection> <br />
<br />
<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>'''Dengue NS3/NS2B Protein'''[[2vbc]]<br />
The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/7'>NS2B</scene>. This cofactor then wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that NS2B acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1864538Sandbox 1k4r2013-11-14T16:15:36Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
'''Dengue Virus Genome''' carries only one single strand of RNA as its genome. This genome only encodes for ten proteins (three structural and seven "production" proteins. The production proteins are useful in aiding the virus penetrating the host cell and help produce new virus structures. The outer membrane of the protein is constructed of 180 copies of the envelope protein, which this membrane helps the virus attach to the host cell membrane. <br />
<br />
[[Image:1ok8 copy.jpg]]'''Figure 1:''' ''This image represents the entire Dengue genome (complete with 180 copies of the envelope protein)''<br />
<br />
<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''><br />
'''Dengue Virus inside Cell'''<br />
When the virus is in its infectious form the surface is smooth (''figure 1''), but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike (or trimer, which allows it to penetrate and fuse with the lysozome membrane of the host cell.<br />
The trimer model of the Dengue virus is extracted in many different ways. The one observed extraction was separated by detergent isolation. The model shows a chloride ion (detergent) liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or <scene name='56/565763/Trimer/3'>fusion loop</scene>, displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. <br />
Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108<br />
</StructureSection><br />
<br />
<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''><br />
'''Dengue NS5 Protein'''<br />
The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine (SAM) ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. The SAM and SAH are useful in aiding in the folding of the active site.<br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <scene name='56/565763/Active_site_gtp/3'>GTP in the binding site</scene> is what allows the Dengue-2-methyltransferase to complete its functions; these functions include translation, transcription and replication processes.</StructureSection> <br />
<br />
<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>'''Dengue NS3/NS2B Protein'''<br />
The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/7'>NS2B</scene>. This cofactor then wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that NS2B acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1864536Sandbox 1k4r2013-11-14T16:15:13Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
'''Dengue Virus Genome''' carries only one single strand of RNA as its genome. This genome only encodes for ten proteins (three structural and seven "production" proteins. The production proteins are useful in aiding the virus penetrating the host cell and help produce new virus structures. The outer membrane of the protein is constructed of 180 copies of the envelope protein, which this membrane helps the virus attach to the host cell membrane. <br />
<br />
[[Image:1ok8 copy.jpg]]'''Figure 1:''' ''This image represents the entire Dengue genome (complete with 180 copies of the envelope protein)''<br />
<br />
<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''><br />
'''Dengue Virus inside Cell'''<br />
When the virus is in its infectious form the surface is smooth (figure 1), but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike (or trimer, which allows it to penetrate and fuse with the lysozome membrane of the host cell.<br />
The trimer model of the Dengue virus is extracted in many different ways. The one observed extraction was separated by detergent isolation. The model shows a chloride ion (detergent) liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or <scene name='56/565763/Trimer/3'>fusion loop</scene>, displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. <br />
Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108<br />
</StructureSection><br />
<br />
<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''><br />
'''Dengue NS5 Protein'''<br />
The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine (SAM) ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. The SAM and SAH are useful in aiding in the folding of the active site.<br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <scene name='56/565763/Active_site_gtp/3'>GTP in the binding site</scene> is what allows the Dengue-2-methyltransferase to complete its functions; these functions include translation, transcription and replication processes.</StructureSection> <br />
<br />
<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>'''Dengue NS3/NS2B Protein'''<br />
The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/7'>NS2B</scene>. This cofactor then wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that NS2B acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1864533Sandbox 1k4r2013-11-14T16:02:25Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
'''Dengue Virus Genome''' carries only one single strand of RNA as its genome. This genome only encodes for ten proteins (three structural and seven "production" proteins. The production proteins are useful in aiding the virus penetrating the host cell and help produce new virus structures. The outer membrane of the protein is constructed of 180 copies of the envelope protein, which this membrane helps the virus attach to the host cell membrane. <br />
<br />
[[Image:1ok8 copy.jpg]]'''Figure 1:''' ''This image represents the entire Dengue genome (complete with 180 copies of the envelope protein)''<br />
<br />
'''Dengue Virus inside Cell'''<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>When the virus is in its infectious form the surface is smooth (figure 1), but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike (or trimer, which allows it to penetrate and fuse with the lysozome membrane of the host cell.<br />
The trimer model of the Dengue virus is extracted in many different ways. The one observed extraction was separated by detergent isolation. The model shows a chloride ion (detergent) liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or <scene name='56/565763/Trimer/3'>fusion loop</scene>, displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. <br />
Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108<br />
</StructureSection><br />
<br />
'''Dengue NS5 Protein'''<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine (SAM) ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. The SAM and SAH are useful in aiding in the folding of the active site.<br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <scene name='56/565763/Active_site_gtp/3'>GTP in the binding site</scene> is what allows the Dengue-2-methyltransferase to complete its functions; these functions include translation, transcription and replication processes.</StructureSection> <br />
<br />
'''Dengue NS3/NS2B Protein'''<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/7'>NS2B</scene>. This cofactor then wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that NS2B acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1864532Sandbox 1k4r2013-11-14T16:01:15Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
'''Dengue Virus Genome''' carries only one single strand of RNA as its genome. This genome only encodes for ten proteins (three structural and seven "production" proteins. The production proteins are useful in aiding the virus penetrating the host cell and help produce new virus structures. The outer membrane of the protein is constructed of 180 copies of the envelope protein, which this membrane helps the virus attach to the host cell membrane. <br />
<br />
[[Image:1ok8 copy.jpg]]''Figure 1: This image represents the entire Dengue genome (complete with 180 copies of the envelope protein)''<br />
<br />
'''Dengue Virus inside Cell'''<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>When the virus is in its infectious form the surface is smooth (figure 1), but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike (or trimer, which allows it to penetrate and fuse with the lysozome membrane of the host cell.<br />
The trimer model of the Dengue virus is extracted in many different ways. The one observed extraction was separated by detergent isolation. The model shows a chloride ion (detergent) liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or <scene name='56/565763/Trimer/3'>fusion loop</scene>, displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. <br />
Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108<br />
</StructureSection><br />
<br />
'''Dengue NS5 Protein'''<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine (SAM) ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. The SAM and SAH are useful in aiding in the folding of the active site.<br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <scene name='56/565763/Active_site_gtp/3'>GTP in the binding site</scene> is what allows the Dengue-2-methyltransferase to complete its functions; these functions include translation, transcription and replication processes.</StructureSection> <br />
<br />
'''Dengue NS3/NS2B Protein'''<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/7'>NS2B</scene>. This cofactor then wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that NS2B acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1864531Sandbox 1k4r2013-11-14T15:59:07Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
'''Dengue Virus Genome''' carries only one single strand of RNA as its genome. This genome only encodes for ten proteins (three structural and seven "production" proteins. The production proteins are useful in aiding the virus penetrating the host cell and help produce new virus structures. The outer membrane of the protein is constructed of 180 copies of the envelope protein, which this membrane helps the virus attach to the host cell membrane. <br />
<br />
[[Image:1ok8 copy.jpg]]''Figure 1: This image represents the entire Dengue genome (complete with 180 copies of the envelope protein)''<br />
<br />
'''Dengue Virus inside Cell'''<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>When the virus is in its infectious form the surface is smooth (figure 1), but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike (or trimer, which allows it to penetrate and fuse with the lysozome membrane of the host cell.<br />
The trimer model of the Dengue virus is extracted in many different ways. The one observed extraction was separated by detergent isolation. The model shows a chloride ion (detergent) liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or <scene name='56/565763/Trimer/3'>fusion loop</scene>, displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. <br />
Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108<br />
</StructureSection><br />
<br />
'''Dengue NS5 Protein'''<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine (SAM) ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. The SAM and SAH are useful in aiding in the folding of the active site.<br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <scene name='56/565763/Active_site_gtp/3'>GTP in the binding site</scene> is what allows the Dengue-2-methyltransferase to complete its functions; these functions include translation, transcription and replication processes.</StructureSection> <br />
<br />
'''Dengue NS3/NS2B Protein'''<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/6'>NS2B</scene>. This cofactor then wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that NS2B acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1864530Sandbox 1k4r2013-11-14T15:50:23Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
'''Dengue Virus Genome''' carries only one single strand of RNA as its genome. This genome only encodes for ten proteins (three structural and seven "production" proteins. The production proteins are useful in aiding the virus penetrating the host cell and help produce new virus structures. The outer membrane of the protein is constructed of 180 copies of the envelope protein, which this membrane helps the virus attach to the host cell membrane. <br />
<br />
[[Image:1ok8 copy.jpg]]''Figure 1: This image represents the entire Dengue genome (complete with 180 copies of the envelope protein)''<br />
<br />
'''Dengue Virus inside Cell'''<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>When the virus is in its infectious form the surface is smooth (figure 1), but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike (or trimer, which allows it to penetrate and fuse with the lysozome membrane of the host cell.<br />
The trimer model of the Dengue virus is extracted in many different ways. The one observed extraction was separated by detergent isolation. The model shows a chloride ion (detergent) liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or <scene name='56/565763/Trimer/3'>fusion loop</scene>, displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. <br />
Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108<br />
</StructureSection><br />
<br />
'''Dengue NS5 Protein'''<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. <br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <scene name='56/565763/Active_site_gtp/3'>GTP in the binding site</scene> is what allows the Dengue-2-methyltransferase to complete its functions; these functions include translation, transcription and replication processes.</StructureSection> <br />
<br />
'''Dengue NS3/NS2B Protein'''<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/5'>NS2B</scene>. This cofactor wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that the NS2B cofactor acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]<br />
<br />
== Headline text ==</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1862024Sandbox 1k4r2013-11-12T14:55:34Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
'''Dengue Virus Genome''' carries only one single strand of RNA as its genome. This genome only encodes for ten proteins (three structural and seven "production" proteins. The production proteins are useful in aiding the virus penetrating the host cell and help produce new virus structures. The outer membrane of the protein is constructed of 180 copies of the envelope protein, which this membrane helps the virus attach to the host cell membrane.<br />
<br />
<br />
<br />
[[Image:1ok8 copy.jpg]] <br />
<br />
Dengue Virus inside Cell<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>When the virus is in its infectious form the surface is smooth, but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike so as to penetrate and then fuze with the lysozome membrane.<br />
The trimer model of the Dengue virus is extracted in many different ways. The one observed experiment was separated by detergent extraction. The model shows a chloride ion liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or <scene name='56/565763/Trimer/3'>fusion loop</scene>, displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. <br />
Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108<br />
</StructureSection><br />
<br />
Dengue NS5 Protein<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. <br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <scene name='56/565763/Active_site_gtp/3'>GTP in the binding site</scene> is to be a cap-binding site for the Dengue-2-methyltransferase. Overall the GTP is required for translation, transcription and replication processes.</StructureSection> <br />
<br />
Dengue NS3/NS2B Protein<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/5'>NS2B</scene>. This cofactor wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that the NS2B cofactor acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]<br />
<br />
== Headline text ==</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=File:1ok8_copy.jpg&diff=1862023File:1ok8 copy.jpg2013-11-12T14:45:19Z<p>Sunjeet Virdi: </p>
<hr />
<div></div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1862014Sandbox 1k4r2013-11-12T14:11:47Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
Dengue Virus inside Cell<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>When the virus is in its infectious form the surface is smooth, but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike so as to penetrate and then fuze with the lysozome membrane.<br />
The trimer model of the Dengue virus is extracted in many different ways. The one observed experiment was separated by detergent extraction. The model shows a chloride ion liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or <scene name='56/565763/Trimer/3'>fusion loop</scene>, displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. <br />
Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108<br />
</StructureSection><br />
<br />
Dengue NS5 Protein<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. <br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <scene name='56/565763/Active_site_gtp/3'>GTP in the binding site</scene> is to be a cap-binding site for the Dengue-2-methyltransferase. Overall the GTP is required for translation, transcription and replication processes.</StructureSection> <br />
<br />
Dengue NS3/NS2B Protein<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/5'>NS2B</scene>. This cofactor wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that the NS2B cofactor acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_vdr&diff=1862012Sandbox vdr2013-11-12T13:59:37Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Vitamin D Receptor ==<br />
<br />
'''Vitamin D receptor''' (<scene name='56/562378/Vit_d_receptor_3m7r/3'>VDR</scene>) is a transcription factor. Upon binding to vitamin D, VDR forms a heterodimer with retinoid-X receptor and binds to hormone response receptors on DNA causing gene expression. VDR contains a ligand binding domain (<scene name='56/562378/Vit_d_receptor_ligand/1'>LBD</scene>) and DNA-binding domain (DBD).<br />
<br />
<br />
{{STRUCTURE_1db1| PDB=1db1 | SCENE= }} <br />
===CRYSTAL STRUCTURE OF THE NUCLEAR RECEPTOR FOR VITAMIN D COMPLEXED TO VITAMIN D===<br />
{{ABSTRACT_PUBMED_10678179}}<br />
<br />
==Disease==<br />
[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[http://omim.org/entry/277440 277440]]. A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.<ref>PMID:2849209</ref><ref>PMID:8381803</ref><ref>PMID:1652893</ref><ref>PMID:2177843</ref><ref>PMID:8106618</ref><ref>PMID:8392085</ref><ref>PMID:7828346</ref><ref>PMID:8675579</ref><ref>PMID:8961271</ref><ref>PMID:9005998</ref> <br />
<br />
==Function==<br />
[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<ref>PMID:16252006</ref><ref>PMID:10678179</ref><ref>PMID:15728261</ref><ref>PMID:16913708</ref> <br />
<br />
==Mutation==<br />
Serine/ threonine kinase plays a crucial role in signal transduction pathways drawn out by variety of growth factors, hormones, and neurotransmitters. When <scene name='56/562378/Vit_d_receptor_3m7r_serine/5'>serine</scene> is mutated it is replaced by with <scene name='56/562378/Vit_d_receptor_3m7r_serine/8'>glycine</scene> which results in an inhibition of transcriptional activation. When transcription is inhibited it results in p53 accumulation, which activates and promotes p53 translocation into mitochondria leading to apoptosis. Transcription inhibition is useful in cancer patients.<br />
<br />
<br />
<scene name='56/562378/Vit_d_receptor_3m7r_serine/5'>Serine</scene> is replaced with <br />
<scene name='56/562378/Vit_d_receptor_3m7r_serine/9'>aspartic acid</scene> when mutated creating a negative charge. The negative charge at the residue inhibits DNA binding which cause a down – regulation of VDR activity. VDR needs DNA binding in order for it to be activated which is only possible with a serine residue.<br />
<br />
==Crystal structure of the human VDR ligand binding domain bound to the synthetic agonist compound 2alpha-methyl-AMCR277A(C23S)==<br />
Research showed that <scene name='56/562378/3a3z/1'>the synthetic analogue (20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (2a)</scene> acts as a 1alpha,25(OH)(2)D(3) superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1alpha,25(OH)(2)D(3), 2alpha-methyl-1alpha,25(OH)(2)D(3), or 2a, we designed a novel analogue, 2alpha-methyl-(20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes. <br />
<br />
<br />
<br />
==About this Structure==<br />
[[1db1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DB1 OCA]. On right hand side is Structure of human vitamin D receptor ligand-binding domain complex with vitamin D (PDB entry [[1db1]]).<br />
<br />
==See Also==<br />
*[[Vitamin D receptor|Vitamin D receptor]]<br />
<br />
<br />
== 3D Structures of vitamin D receptor==<br />
<br />
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}<br />
<br />
===Vitamin D receptor ligand-binding domain===<br />
<br />
[[3m7r]] - hVDR LBD (mutant) – human<br /><br />
<br />
[[1db1]] – hVDR LBD + vitamin D <br /><br />
[[1s0z]], [[1s19]], [[3a78]], [[4g2i]] - hVDR LBD + vitamin D derivative<br /><br />
[[3ogt]], [[2ham]], [[2har]], [[2has]], [[2hb7]], [[2hb8]], [[3p8x]], [[3az1]], [[3az2]], [[3az3]], [[3tkc]] - hVDR LBD + vitamin D analog<br /><br />
[[3auq]], [[3aur]], [[3kpz]] - hVDR LBD (mutant) + vitamin D analog<br /><br />
[[3a2i]], [[3a2j]], [[3b0t]], [[3ax8]], [[3vhw]] - hVDR LBD (mutant) + vitamin D derivative<br /><br />
[[3a3z]], [[3a40]] - hVDR LBD + agonist<br /><br />
[[1ie8]], [[1ie9]], [[3cs4]], [[3cs6]], [[1txi]] – hVDR LBD + superagonist <br /><br />
[[3w5q]], [[3w5r]], [[3w5t]] - hVDR LBD + lithocholic acid derivative <br /><br />
<br />
''Vitamin D receptor LBD complex with peptide''<br />
<br />
[[1rjk]], [[1rk3]], [[1rkg]], [[1rkh]], [[2o4j]], [[2o4r]] – rVDR LBD (mutant) + peroxisome proliferator-activated receptor peptide – rat<br /><br />
[[2zl9]], [[2zla]], [[2zlc]] - rVDR LBD + coactivator peptide DRIP + vitamin D analog<br /><br />
[[3vrt]], [[3vru]], [[3vrv]], [[3vrw]] - rVDR LBD (mutant) + coactivator peptide DRIP + vitamin D analog<br /><br />
[[2zfx]], [[3a2h]], [[2zxm]], [[2zxn]] - rVDR LBD + coactivator peptide DRIP<br /><br />
[[3aun]], [[2zmh]], [[2zmi]], [[2zmj]], [[3afr]], [[3vjs]], [[3vjt]] - rVDR LBD (mutsant) + coactivator peptide DRIP<br /><br />
[[2hbh]] - zVDR LBD + steroid receptor coactivator 1 peptide – zebrafish<br /><br />
[[2hc4]] - zVDR LBD + steroid receptor coactivator 1 peptide + vitamin D<br /><br />
[[2hcd]] - zVDR LBD + steroid receptor coactivator 1 peptide <br />
<br />
===Vitamin D receptor DNA-binding domain===<br />
<br />
[[1kb2]] – hVDR DBD + osteopontin response element DNA<br /><br />
[[1kb4]] – hVDR DBD + DR3 response element DNA<br /><br />
[[1ynw]] – hVDR DBD (mutant) + DR3 response element DNA<br /><br />
[[1kb6]] – hVDR DBD + osteocalcin response element DNA<br /><br />
<br />
</StructureSection><br />
[[Category:Topic Page]]<br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:010678179</ref><ref group="xtra">PMID:011344298</ref><references group="xtra"/><references/><br />
[[Category: Homo sapiens]]<br />
[[Category: Klaholz, B.]]<br />
[[Category: Mitschler, A.]]<br />
[[Category: Moras, D.]]<br />
[[Category: Rochel, N.]]<br />
[[Category: Wurtz, J M.]]<br />
[[Category: Complex]]<br />
[[Category: Gene regulation]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_vdr&diff=1862011Sandbox vdr2013-11-12T13:54:36Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Vitamin D Receptor ==<br />
<br />
'''Vitamin D receptor''' (<scene name='56/562378/Vit_d_receptor_3m7r/3'>VDR</scene>) is a transcription factor. Upon binding to vitamin D, VDR forms a heterodimer with retinoid-X receptor and binds to hormone response receptors on DNA causing gene expression. VDR contains a ligand binding domain (<scene name='56/562378/Vit_d_receptor_ligand/1'>LBD</scene>) and DNA-binding domain (DBD).<br />
<br />
<br />
{{STRUCTURE_1db1| PDB=1db1 | SCENE= }} <br />
===CRYSTAL STRUCTURE OF THE NUCLEAR RECEPTOR FOR VITAMIN D COMPLEXED TO VITAMIN D===<br />
{{ABSTRACT_PUBMED_10678179}}<br />
<br />
==Disease==<br />
[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[http://omim.org/entry/277440 277440]]. A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.<ref>PMID:2849209</ref><ref>PMID:8381803</ref><ref>PMID:1652893</ref><ref>PMID:2177843</ref><ref>PMID:8106618</ref><ref>PMID:8392085</ref><ref>PMID:7828346</ref><ref>PMID:8675579</ref><ref>PMID:8961271</ref><ref>PMID:9005998</ref> <br />
<br />
==Function==<br />
[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<ref>PMID:16252006</ref><ref>PMID:10678179</ref><ref>PMID:15728261</ref><ref>PMID:16913708</ref> <br />
<br />
==Mutation==<br />
Serine/ threonine kinase plays a crucial role in signal transduction pathways drawn out by variety of growth factors, hormones, and neurotransmitters. When <scene name='56/562378/Vit_d_receptor_3m7r_serine/5'>serine</scene> is mutated it is replaced by with <scene name='56/562378/Vit_d_receptor_3m7r_serine/8'>glycine</scene> which results in an inhibition of transcriptional activation. When transcription is inhibited it results in p53 accumulation, which activates and promotes p53 translocation into mitochondria leading to apoptosis. Transcription inhibition is useful in cancer patients.<br />
<br />
<br />
<scene name='56/562378/Vit_d_receptor_3m7r_serine/5'>Serine</scene> is replaced with aspartic acid when mutated creating a negative charge. The negative charge at the residue inhibits DNA binding which cause a down – regulation of VDR activity. VDR needs DNA binding in order for it to be activated which is only possible with a serine residue.<br />
<br />
==Crystal structure of the human VDR ligand binding domain bound to the synthetic agonist compound 2alpha-methyl-AMCR277A(C23S)==<br />
Research showed that <scene name='56/562378/3a3z/1'>the synthetic analogue (20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (2a)</scene> acts as a 1alpha,25(OH)(2)D(3) superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1alpha,25(OH)(2)D(3), 2alpha-methyl-1alpha,25(OH)(2)D(3), or 2a, we designed a novel analogue, 2alpha-methyl-(20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes. <br />
<br />
<br />
<br />
==About this Structure==<br />
[[1db1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DB1 OCA]. On right hand side is Structure of human vitamin D receptor ligand-binding domain complex with vitamin D (PDB entry [[1db1]]).<br />
<br />
==See Also==<br />
*[[Vitamin D receptor|Vitamin D receptor]]<br />
<br />
<br />
== 3D Structures of vitamin D receptor==<br />
<br />
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}<br />
<br />
===Vitamin D receptor ligand-binding domain===<br />
<br />
[[3m7r]] - hVDR LBD (mutant) – human<br /><br />
<br />
[[1db1]] – hVDR LBD + vitamin D <br /><br />
[[1s0z]], [[1s19]], [[3a78]], [[4g2i]] - hVDR LBD + vitamin D derivative<br /><br />
[[3ogt]], [[2ham]], [[2har]], [[2has]], [[2hb7]], [[2hb8]], [[3p8x]], [[3az1]], [[3az2]], [[3az3]], [[3tkc]] - hVDR LBD + vitamin D analog<br /><br />
[[3auq]], [[3aur]], [[3kpz]] - hVDR LBD (mutant) + vitamin D analog<br /><br />
[[3a2i]], [[3a2j]], [[3b0t]], [[3ax8]], [[3vhw]] - hVDR LBD (mutant) + vitamin D derivative<br /><br />
[[3a3z]], [[3a40]] - hVDR LBD + agonist<br /><br />
[[1ie8]], [[1ie9]], [[3cs4]], [[3cs6]], [[1txi]] – hVDR LBD + superagonist <br /><br />
[[3w5q]], [[3w5r]], [[3w5t]] - hVDR LBD + lithocholic acid derivative <br /><br />
<br />
''Vitamin D receptor LBD complex with peptide''<br />
<br />
[[1rjk]], [[1rk3]], [[1rkg]], [[1rkh]], [[2o4j]], [[2o4r]] – rVDR LBD (mutant) + peroxisome proliferator-activated receptor peptide – rat<br /><br />
[[2zl9]], [[2zla]], [[2zlc]] - rVDR LBD + coactivator peptide DRIP + vitamin D analog<br /><br />
[[3vrt]], [[3vru]], [[3vrv]], [[3vrw]] - rVDR LBD (mutant) + coactivator peptide DRIP + vitamin D analog<br /><br />
[[2zfx]], [[3a2h]], [[2zxm]], [[2zxn]] - rVDR LBD + coactivator peptide DRIP<br /><br />
[[3aun]], [[2zmh]], [[2zmi]], [[2zmj]], [[3afr]], [[3vjs]], [[3vjt]] - rVDR LBD (mutsant) + coactivator peptide DRIP<br /><br />
[[2hbh]] - zVDR LBD + steroid receptor coactivator 1 peptide – zebrafish<br /><br />
[[2hc4]] - zVDR LBD + steroid receptor coactivator 1 peptide + vitamin D<br /><br />
[[2hcd]] - zVDR LBD + steroid receptor coactivator 1 peptide <br />
<br />
===Vitamin D receptor DNA-binding domain===<br />
<br />
[[1kb2]] – hVDR DBD + osteopontin response element DNA<br /><br />
[[1kb4]] – hVDR DBD + DR3 response element DNA<br /><br />
[[1ynw]] – hVDR DBD (mutant) + DR3 response element DNA<br /><br />
[[1kb6]] – hVDR DBD + osteocalcin response element DNA<br /><br />
<br />
</StructureSection><br />
[[Category:Topic Page]]<br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:010678179</ref><ref group="xtra">PMID:011344298</ref><references group="xtra"/><references/><br />
[[Category: Homo sapiens]]<br />
[[Category: Klaholz, B.]]<br />
[[Category: Mitschler, A.]]<br />
[[Category: Moras, D.]]<br />
[[Category: Rochel, N.]]<br />
[[Category: Wurtz, J M.]]<br />
[[Category: Complex]]<br />
[[Category: Gene regulation]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1861935Sandbox 1k4r2013-11-11T20:26:21Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
Dengue Virus inside Cell<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>When the virus is in its infectious form the surface is smooth, but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike so as to penetrate and then fuze with the lysozome membrane.<br />
The trimer model of the Dengue virus is extracted in many different ways. The one observed experiment was separated by detergent extraction. The model shows a chloride ion liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or <scene name='56/565763/Trimer/3'>fusion loop</scene>, displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. <br />
Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108<br />
</StructureSection><br />
<br />
Dengue NS5 Protein<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. <br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <scene name='56/565763/Active_site_gtp/3'>GTP in the binding site</scene> is to be a cap-binding site for the Dengue-2-methyltransferase. Overall the GTP is required for translation, transcription and replication processes.</StructureSection> <br />
<br />
Dengue NS3/NS2B Protein<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/2'>NS2B</scene>. This cofactor wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that the NS2B cofactor acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1859802Sandbox 1k4r2013-11-05T15:39:34Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
Dengue Virus inside Cell<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>When the virus is in its infectious form the surface is smooth, but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike so as to penetrate and then fuze with the lysozome membrane.<br />
After the lysozome membrane has been penetrated the RNA is injected and the infection begins<br />
After a person is infected with dengue, they develop an immune response that produces specific antibodies that prevent the virus from binding to macrophage cells and gaining entry. <br />
However, if another subtype of dengue virus infects the individual, the virus will activate the immune system to attack it as if it was the first subtype, producing the same antibodies as before, unfortunately these do not work on the subtype.<br />
The immune system is tricked because the four subtypes have very similar surface antigens. The antibodies bind to the surface proteins but do not inactivate the virus.<br />
The human body is dependant on the right antibody response, and because it is not the right response the virus is not inactivated.<br />
The immune response attracts numerous macrophages and the virus proceeds to infect them.<br />
This makes the viral infection much more acute, and the body begins to release cytokines (small cell-signaling protein molecules that are secreted by the glial cells of the nervous system) which causes the endothelial tissues (the layer of cells lining the interior surface of all blood vessels, from the heart to the smallest capillary) to become permeable, it then turns into Dengue Haemorrhagic Fever, which is deadly.<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike, as shown at the bottom from PDB entry 1ok8. Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome. This releases the RNA into the cell and infection starts. The hemagglutinin protein on the surface of influenza virus plays a similar role, but the two proteins use entirely different mechanisms to perform a similar task.<br />
</StructureSection><br />
<br />
Dengue NS5 Protein<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<br />
Dengue-2 NS5 contains an also has an <scene name='56/565763/Sah/4'>active site</scene> which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine (<scene name='56/565763/Sah/5'>SAH</scene>)as a by-product. <br />
In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The <scene name='56/565763/Active_site_gtp/3'>GTP in the binding site</scene> is to be a cap-binding site for the Dengue-2-methyltransferase. Overall the GTP is required for translation, transcription and replication processes.</StructureSection> <br />
<br />
Dengue NS3/NS2B Protein<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/2'>NS2B</scene>. This cofactor wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that the NS2B cofactor acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1859787Sandbox 1k4r2013-11-05T14:20:56Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
Dengue Virus inside Cell<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>When the virus is in its infectious form the surface is smooth, but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike so as to penetrate and then fuze with the lysozome membrane.<br />
After the lysozome membrane has been penetrated the RNA is injected and the infection begins<br />
After a person is infected with dengue, they develop an immune response that produces specific antibodies that prevent the virus from binding to macrophage cells and gaining entry. <br />
However, if another subtype of dengue virus infects the individual, the virus will activate the immune system to attack it as if it was the first subtype, producing the same antibodies as before, unfortunately these do not work on the subtype.<br />
The immune system is tricked because the four subtypes have very similar surface antigens. The antibodies bind to the surface proteins but do not inactivate the virus.<br />
The human body is dependant on the right antibody response, and because it is not the right response the virus is not inactivated.<br />
The immune response attracts numerous macrophages and the virus proceeds to infect them.<br />
This makes the viral infection much more acute, and the body begins to release cytokines (small cell-signaling protein molecules that are secreted by the glial cells of the nervous system) which causes the endothelial tissues (the layer of cells lining the interior surface of all blood vessels, from the heart to the smallest capillary) to become permeable, it then turns into Dengue Haemorrhagic Fever, which is deadly.<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike, as shown at the bottom from PDB entry 1ok8. Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome. This releases the RNA into the cell and infection starts. The hemagglutinin protein on the surface of influenza virus plays a similar role, but the two proteins use entirely different mechanisms to perform a similar task.<br />
</StructureSection><br />
<br />
Dengue NS5 Protein<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase. The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation.<br />
There are four serotypes of the Dengue virus, and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis.<scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene><scene name='56/565763/Sah/1'>NS5</scene></StructureSection><scene name='56/565763/Sah/3'>SAM</scene><scene name='56/565763/Sah/4'>Active Site</scene><br />
<br />
Dengue NS3/NS2B Protein<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad <scene name='56/565763/Ns2b/3'>(His-51, Asp-75 and Ser-135)</scene>, is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/2'>NS2B</scene>. This cofactor wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that the NS2B cofactor acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1859775Sandbox 1k4r2013-11-05T03:39:45Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
Dengue Virus inside Cell<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>When the virus is in its infectious form the surface is smooth, but as it is exposed to the acidic environment of the cell causes the proteins to snap into a trimeric spike so as to penetrate and then fuze with the lysozome membrane.<br />
After the lysozome membrane has been penetrated the RNA is injected and the infection begins<br />
After a person is infected with dengue, they develop an immune response that produces specific antibodies that prevent the virus from binding to macrophage cells and gaining entry. <br />
However, if another subtype of dengue virus infects the individual, the virus will activate the immune system to attack it as if it was the first subtype, producing the same antibodies as before, unfortunately these do not work on the subtype.<br />
The immune system is tricked because the four subtypes have very similar surface antigens. The antibodies bind to the surface proteins but do not inactivate the virus.<br />
The human body is dependant on the right antibody response, and because it is not the right response the virus is not inactivated.<br />
The immune response attracts numerous macrophages and the virus proceeds to infect them.<br />
This makes the viral infection much more acute, and the body begins to release cytokines (small cell-signaling protein molecules that are secreted by the glial cells of the nervous system) which causes the endothelial tissues (the layer of cells lining the interior surface of all blood vessels, from the heart to the smallest capillary) to become permeable, it then turns into Dengue Haemorrhagic Fever, which is deadly.<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike, as shown at the bottom from PDB entry 1ok8. Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome. This releases the RNA into the cell and infection starts. The hemagglutinin protein on the surface of influenza virus plays a similar role, but the two proteins use entirely different mechanisms to perform a similar task.<br />
</StructureSection><br />
<br />
Dengue NS5 Protein<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The N-terminal domain has the capacity to bind GTP, hold the guanosine of the viral cap structure, and synthesize two different methylation reactions that are required for the formation of the RNA cap (3). A GTP-binding site in the N-terminal domain is suggested to be a cap-binding site for the Dengue-2-methyltransferase (4). The C-terminal subdomain is an RNA-dependent-RNA polymerase (RdRp) domain. The core subunit is responsible for Ado-Met binding and catalytic activity due to the GTP-binding pocket (3).<scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene><scene name='56/565763/Sah/1'>NS5</scene></StructureSection><br />
<br />
Dengue NS3/NS2B Protein<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad (His-51, Asp-75 and Ser-135), is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/2'>NS2B</scene>. This cofactor wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that the NS2B cofactor acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1859773Sandbox 1k4r2013-11-05T03:37:42Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
Dengue Virus inside Cell<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><br />
<br />
Dengue NS5 Protein<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The N-terminal domain has the capacity to bind GTP, hold the guanosine of the viral cap structure, and synthesize two different methylation reactions that are required for the formation of the RNA cap (3). A GTP-binding site in the N-terminal domain is suggested to be a cap-binding site for the Dengue-2-methyltransferase (4). The C-terminal subdomain is an RNA-dependent-RNA polymerase (RdRp) domain. The core subunit is responsible for Ado-Met binding and catalytic activity due to the GTP-binding pocket (3).<scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene><scene name='56/565763/Sah/1'>NS5</scene></StructureSection><br />
<br />
Dengue NS3/NS2B Protein<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad (His-51, Asp-75 and Ser-135), is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/2'>NS2B</scene>. This cofactor wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that the NS2B cofactor acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1859772Sandbox 1k4r2013-11-05T03:35:50Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<br />
<br />
<br />
<br />
==Dengue Virus inside Cell==<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><br />
<br />
Dengue NS5 Protein<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The N-terminal domain has the capacity to bind GTP, hold the guanosine of the viral cap structure, and synthesize two different methylation reactions that are required for the formation of the RNA cap (3). A GTP-binding site in the N-terminal domain is suggested to be a cap-binding site for the Dengue-2-methyltransferase (4). The C-terminal subdomain is an RNA-dependent-RNA polymerase (RdRp) domain. The core subunit is responsible for Ado-Met binding and catalytic activity due to the GTP-binding pocket (3).<scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene><scene name='56/565763/Sah/1'>NS5</scene></StructureSection><br />
<br />
Dengue NS3/NS2B Protein<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad (His-51, Asp-75 and Ser-135), is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/2'>NS2B</scene>. This cofactor wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that the NS2B cofactor acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1859770Sandbox 1k4r2013-11-05T03:35:11Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<br />
<br />
<br />
<br />
==Dengue Virus inside Cell==<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><br />
<br />
Dengue NS3 Protein<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The N-terminal domain has the capacity to bind GTP, hold the guanosine of the viral cap structure, and synthesize two different methylation reactions that are required for the formation of the RNA cap (3). A GTP-binding site in the N-terminal domain is suggested to be a cap-binding site for the Dengue-2-methyltransferase (4). The C-terminal subdomain is an RNA-dependent-RNA polymerase (RdRp) domain. The core subunit is responsible for Ado-Met binding and catalytic activity due to the GTP-binding pocket (3).<scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene><scene name='56/565763/Sah/1'>NS5</scene></StructureSection><br />
<br />
Dengue NS5 Protein<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad (His-51, Asp-75 and Ser-135), is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/2'>NS2B</scene>. This cofactor wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that the NS2B cofactor acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1859767Sandbox 1k4r2013-11-05T03:24:27Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<br />
<br />
<br />
<br />
==Dengue Virus inside Cell==<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><br />
<br />
==GTP to Methyltransferase==<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The N-terminal domain has the capacity to bind GTP, hold the guanosine of the viral cap structure, and synthesize two different methylation reactions that are required for the formation of the RNA cap (3). A GTP-binding site in the N-terminal domain is suggested to be a cap-binding site for the Dengue-2-methyltransferase (4). The C-terminal subdomain is an RNA-dependent-RNA polymerase (RdRp) domain. The core subunit is responsible for Ado-Met binding and catalytic activity due to the GTP-binding pocket (3).<scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene>.</StructureSection><br />
<br />
==Dengue Methyltransferase==<StructureSection load='1l9k' size='500' side='right' caption='NS5 methyltransferase (PDB entry [[1l9k]])' scene=''>Dengue-2 NS5 methyltransferase is one of the seven nonstructural proteins in the polyprotein encoded by the flavivirus genome's single open reading frame. This is the non-structural protein, NS5, which is the largest and most conserved protein in a flavivirus.The Dengue-2-virus methyltransferase has an N-terminal subdomain, a core subdomain, a C-terminal subdomain (3) and a K-D-K-E motif (9). Dengue-2 NS5 methyltransferase also has an "S-adenosyl methionine-dependent methyltransferase fold" structure which is essentially a "sandwich" of αβα sheets in the N-terminal domain<scene name='56/565763/Sah/1'>NS5</scene></StructureSection><br />
<br />
<br />
Dengue Protease and Helicase<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. <br />
The catalytic triad (His-51, Asp-75 and Ser-135), is found between these two β-barrels, and its activity is dependent on the presence of the <scene name='56/565763/Ns2b/2'>NS2B</scene>. This cofactor wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that the NS2B cofactor acts as an enzyme activator as well as being directly involved in substrate binding/interactions.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1859219Sandbox 1k4r2013-10-30T17:18:48Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<br />
<br />
<br />
<br />
==Dengue Virus inside Cell==<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><br />
<br />
==GTP to Methyltransferase==<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The N-terminal domain has the capacity to bind GTP, hold the guanosine of the viral cap structure, and synthesize two different methylation reactions that are required for the formation of the RNA cap (3). A GTP-binding site in the N-terminal domain is suggested to be a cap-binding site for the Dengue-2-methyltransferase (4). The C-terminal subdomain is an RNA-dependent-RNA polymerase (RdRp) domain. The core subunit is responsible for Ado-Met binding and catalytic activity due to the GTP-binding pocket (3).<scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene>.</StructureSection><br />
<br />
==Dengue Methyltransferase==<StructureSection load='1l9k' size='500' side='right' caption='NS5 methyltransferase (PDB entry [[1l9k]])' scene=''>Dengue-2 NS5 methyltransferase is one of the seven nonstructural proteins in the polyprotein encoded by the flavivirus genome's single open reading frame. This is the non-structural protein, NS5, which is the largest and most conserved protein in a flavivirus.The Dengue-2-virus methyltransferase has an N-terminal subdomain, a core subdomain, a C-terminal subdomain (3) and a K-D-K-E motif (9). Dengue-2 NS5 methyltransferase also has an "S-adenosyl methionine-dependent methyltransferase fold" structure which is essentially a "sandwich" of αβα sheets in the N-terminal domain<scene name='56/565763/Sah/1'>NS5</scene></StructureSection><br />
<br />
<br />
==Dengue Protease and Helicase==<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''>The NS2B cofactor is critical for proteolytic activation of the flavivirus NS3 protease. To elucidate the<br />
mechanism involved in NS2B-mediated activation of NS3 protease, molecular dynamic simulation, principal<br />
component analysis, molecular docking, mutagenesis, and bioassay studies were carried out on both the dengue<br />
virus NS3pro and NS2B-NS3pro systems. <scene name='56/565763/Ns2b/2'>NS2B</scene>.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1859215Sandbox 1k4r2013-10-30T17:07:05Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<br />
<br />
<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The N-terminal domain has the capacity to bind GTP, hold the guanosine of the viral cap structure, and synthesize two different methylation reactions that are required for the formation of the RNA cap (3). A GTP-binding site in the N-terminal domain is suggested to be a cap-binding site for the Dengue-2-methyltransferase (4). The C-terminal subdomain is an RNA-dependent-RNA polymerase (RdRp) domain. The core subunit is responsible for Ado-Met binding and catalytic activity due to the GTP-binding pocket (3).<scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene>.</StructureSection><br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1l9k' size='500' side='right' caption='NS5 methyltransferase (PDB entry [[1l9k]])' scene=''><scene name='56/565763/Sah/1'>TextToBeDisplayed</scene></StructureSection><br />
<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''><scene name='56/565763/Ns2b/2'>NS2B</scene>.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1859214Sandbox 1k4r2013-10-30T17:06:36Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<br />
<br />
<br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''>The N-terminal domain has the capacity to bind GTP, hold the guanosine of the viral cap structure, and synthesize two different methylation reactions that are required for the formation of the RNA cap (3). A GTP-binding site in the N-terminal domain is suggested to be a cap-binding site for the Dengue-2-methyltransferase (4). The C-terminal subdomain is an RNA-dependent-RNA polymerase (RdRp) domain. The core subunit is responsible for Ado-Met binding and catalytic activity due to the GTP-binding pocket (3).<scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene>.</StructureSection><br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1l9k' size='500' side='right' caption='NS5 methyltransferase (PDB entry [[1l9k]])' scene=''><scene name='56/565763/Sah/1'>TextToBeDisplayed</scene></StructureSection><br />
<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''><scene name='56/565763/Ns2b/2'>NS2B</scene>.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1857053Sandbox 1k4r2013-10-24T03:20:57Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<br />
<br />
<br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1ok8' size='500' side='right' caption='Dengue virus inside cell (PDB entry [[1ok8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''><scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene>.</StructureSection><br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1l9k' size='500' side='right' caption='NS5 methyltransferase (PDB entry [[1l9k]])' scene=''><scene name='56/565763/Sah/1'>TextToBeDisplayed</scene></StructureSection><br />
<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''><scene name='56/565763/Ns2b/2'>NS2B</scene>.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1857052Sandbox 1k4r2013-10-24T03:03:38Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
{{STRUCTURE_1ok8| PDB=1ok8 | SCENE= }} <br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<br />
<br />
<br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''><scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene>.</StructureSection><br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1l9k' size='500' side='right' caption='NS5 methyltransferase (PDB entry [[1l9k]])' scene=''><scene name='56/565763/Sah/1'>TextToBeDisplayed</scene></StructureSection><br />
<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''><scene name='56/565763/Ns2b/2'>NS2B</scene>.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1857051Sandbox 1k4r2013-10-24T02:56:12Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
{{STRUCTURE_1ok8| PDB=1ok8 | SCENE= }} <br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<br />
<br />
<br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''><scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene>.</StructureSection><br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1l9k' size='500' side='right' caption='NS5 methyltransferase (PDB entry [[1l9k]])' scene=''></StructureSection><br />
<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''><scene name='56/565763/Ns2b/2'>NS2B</scene>.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1857050Sandbox 1k4r2013-10-24T02:54:52Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
{{STRUCTURE_1ok8| PDB=1ok8 | SCENE= }} <br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<br />
<br />
<br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''><scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene>.</StructureSection><br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1l9k' size='500' side='right' caption='NS5 methyltransferase (PDB entry [[1l9k]])' scene=''><br />
<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''><scene name='56/565763/Ns2b/2'>NS2B</scene>.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1857049Sandbox 1k4r2013-10-24T02:51:35Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
{{STRUCTURE_1ok8| PDB=1ok8 | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<br />
<br />
<br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''><scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene>.</StructureSection><br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1l9k' size='500' side='right' caption='NS5 methyltransferase (PDB entry [[1l9k]])' scene=''><br />
<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2vbc' size='500' side='right' caption='Structure of protease and helicase (PDB entry [[2vbc]])' scene=''><scene name='56/565763/Ns2b/2'>NS2B</scene>.</StructureSection><br />
<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1857048Sandbox 1k4r2013-10-24T02:49:27Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
{{STRUCTURE_1ok8| PDB=1ok8 | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<br />
<br />
<br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''><scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene>.</StructureSection><br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1l9k' size='500' side='right' caption='NS5 methyltransferase (PDB entry [[1l9k]])' scene=''><br />
<scene name='56/565763/Ns2b/2'>NS2B</scene>.</StructureSection><br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1857047Sandbox 1k4r2013-10-24T02:48:05Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
{{STRUCTURE_1ok8| PDB=1ok8 | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<br />
<br />
<scene name='56/565763/Ns2b/2'>NS2B</scene><br />
<br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2j7w' size='500' side='right' caption='NS5 polymerase (PDB entry [[2j7w]])' scene=''><scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene>.</StructureSection><br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1l9k' size='500' side='right' caption='NS5 methyltransferase (PDB entry [[1l9k]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1857046Sandbox 1k4r2013-10-24T02:46:03Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
{{STRUCTURE_1ok8| PDB=1ok8 | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<br />
<br />
<scene name='56/565763/Ns2b/2'>NS2B</scene><br />
<br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='2j7w' size='500' side='right' caption='NS2B (PDB entry [[2j7w]])' scene=''><scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene>.</StructureSection><br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1857045Sandbox 1k4r2013-10-24T02:44:08Z<p>Sunjeet Virdi: /* About this Structure */</p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
{{STRUCTURE_1ok8| PDB=1ok8 | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus<br />
<br />
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. <br />
high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis<br />
<scene name='56/565763/Active_site_gtp/1'>GTP in active site</scene><br />
<br />
<scene name='56/565763/Ns2b/2'>NS2B</scene><br />
<br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1ok8' size='500' side='right' caption='NS2B (PDB entry [[1ok8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1857044Sandbox 1k4r2013-10-24T01:30:52Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
{{STRUCTURE_1ok8| PDB=1ok8 | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
<br />
<scene name='56/565763/Ns2b/2'>NS2B</scene><br />
<br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1ok8' size='500' side='right' caption='NS2B (PDB entry [[1ok8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1854828Sandbox 1k4r2013-10-23T03:49:33Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike<br />
Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome.<br />
<br />
<scene name='56/565763/Ns2b/2'>NS2B</scene><br />
<br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1854826Sandbox 1k4r2013-10-23T03:44:05Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
<br />
<br />
<scene name='56/565763/Ns2b/2'>NS2B</scene><br />
<br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1854814Sandbox 1k4r2013-10-23T03:29:49Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.<br />
==About this Structure==<br />
<br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1854809Sandbox 1k4r2013-10-23T03:21:19Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
Dengue is caused by any one of four related viruses transmitted by mosquitoes. There are not yet any vaccines to prevent infection with dengue virus (DENV) and the most effective protective measures are those that avoid mosquito bites. When infected, early recognition and prompt supportive treatment can substantially lower the risk of developing severe disease.<br />
==About this Structure==<br />
[[1k4r]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Viruses Viruses]. The July 2008 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Dengue Virus'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2008_7 10.2210/rcsb_pdb/mom_2008_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K4R OCA]. <br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1854808Sandbox 1k4r2013-10-23T03:20:01Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
==About this Structure==<br />
[[1k4r]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Viruses Viruses]. The July 2008 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Dengue Virus'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2008_7 10.2210/rcsb_pdb/mom_2008_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K4R OCA]. <br />
[[Image:1k4rVirion.png|200px]]<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1854803Sandbox 1k4r2013-10-23T03:12:51Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
===Etiology===<br />
==About this Structure==<br />
[[1k4r]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Viruses Viruses]. The July 2008 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Dengue Virus'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2008_7 10.2210/rcsb_pdb/mom_2008_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K4R OCA]. <br />
[[Image:1k4rVirion.png|left|200px]]<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1854801Sandbox 1k4r2013-10-23T03:11:28Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
===Etiology===<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
<br />
==About this Structure==<br />
[[1k4r]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Viruses Viruses]. The July 2008 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Dengue Virus'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2008_7 10.2210/rcsb_pdb/mom_2008_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K4R OCA]. <br />
[[Image:1k4rVirion.png|left|200px]]<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1854797Sandbox 1k4r2013-10-23T03:06:49Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
===Etiology===<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
<br />
==About this Structure==<br />
[[1k4r]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Viruses Viruses]. The July 2008 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Dengue Virus'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2008_7 10.2210/rcsb_pdb/mom_2008_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K4R OCA]. <br />
[[Image:1k4r1.png|left|200px]]<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1854788Sandbox 1k4r2013-10-23T02:54:03Z<p>Sunjeet Virdi: </p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
===Etiology===<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
<br />
==About this Structure==<br />
[[1k4r]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Viruses Viruses]. The July 2008 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Dengue Virus'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2008_7 10.2210/rcsb_pdb/mom_2008_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K4R OCA]. <br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1k4r&diff=1854785Sandbox 1k4r2013-10-23T02:49:26Z<p>Sunjeet Virdi: New page: == Dengue Virus == 200px {{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} ===Structure of Dengue Virus=== {{ABSTRACT_PUBMED_11893341}} ==About this Structure== [[1k4...</p>
<hr />
<div>== Dengue Virus ==<br />
[[Image:1k4r.png|left|200px]]<br />
<br />
{{STRUCTURE_1k4r| PDB=1k4r | SCENE= }} <br />
<br />
===Structure of Dengue Virus===<br />
<br />
{{ABSTRACT_PUBMED_11893341}}<br />
<br />
==About this Structure==<br />
[[1k4r]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Viruses Viruses]. The July 2008 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Dengue Virus'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2008_7 10.2210/rcsb_pdb/mom_2008_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K4R OCA]. <br />
<br />
==Reference==<br />
<ref group="xtra">PMID:011893341</ref><references group="xtra"/><br />
[[Category: Dengue Virus]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Viruses]]<br />
[[Category: Baker, T S.]]<br />
[[Category: Chipman, P R.]]<br />
[[Category: Corver, J.]]<br />
[[Category: Jones, C T.]]<br />
[[Category: Kuhn, R J.]]<br />
[[Category: Lenches, E.]]<br />
[[Category: Mukhopadhyay, S.]]<br />
[[Category: Pletnev, S V.]]<br />
[[Category: Rossmann, M G.]]<br />
[[Category: Strauss, E G.]]<br />
[[Category: Strauss, J H.]]<br />
[[Category: Zhang, W.]]<br />
[[Category: Dengue virus]]<br />
[[Category: Flaviviridae]]<br />
[[Category: Flavivirus]]<br />
[[Category: Glycoprotein e from tick-borne encephalitis virus]]<br />
[[Category: Icosahedral virus]]<br />
[[Category: Virus]]</div>Sunjeet Virdihttps://proteopedia.org/index.php?title=Sandbox_1mel&diff=1854778Sandbox 1mel2013-10-23T02:23:31Z<p>Sunjeet Virdi: New page: == Dromedary Nanobody == 200px {{STRUCTURE_1mel| PDB=1mel | SCENE= }} ===CRYSTAL STRUCTURE OF A CAMEL SINGLE-DOMAIN VH ANTIBODY FRAGMENT IN COMPLEX WITH LY...</p>
<hr />
<div>== Dromedary Nanobody ==<br />
<br />
<br />
[[Image:1mel.png|left|200px]]<br />
<br />
{{STRUCTURE_1mel| PDB=1mel | SCENE= }} <br />
<br />
===CRYSTAL STRUCTURE OF A CAMEL SINGLE-DOMAIN VH ANTIBODY FRAGMENT IN COMPLEX WITH LYSOZYME===<br />
<br />
{{ABSTRACT_PUBMED_8784355}}<br />
<br />
==About this Structure==<br />
[[1mel]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Camelus_dromedarius Camelus dromedarius] and [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. The April 2011 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Nanobodies'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2011_4 10.2210/rcsb_pdb/mom_2011_4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MEL OCA]. <br />
<br />
==See Also==<br />
*[[Hen Egg-White (HEW) Lysozyme|Hen Egg-White (HEW) Lysozyme]]<br />
<br />
==Reference==<br />
<ref group="xtra">PMID:008784355</ref><references group="xtra"/><br />
[[Category: Camelus dromedarius]]<br />
[[Category: Gallus gallus]]<br />
[[Category: Lysozyme]]<br />
[[Category: Nanobodies]]<br />
[[Category: RCSB PDB Molecule of the Month]]<br />
[[Category: Desmyter, A.]]<br />
[[Category: Gharoudi, M Arbabi.]]<br />
[[Category: Hamers, R.]]<br />
[[Category: Muyldermans, S.]]<br />
[[Category: Poortmans, F.]]<br />
[[Category: Thi, M Dao.]]<br />
[[Category: Transue, T R.]]<br />
[[Category: Wyns, L.]]<br />
[[Category: Camel single-domain anti-lysozyme]]</div>Sunjeet Virdi