5t6f

From Proteopedia

(Difference between revisions)

Revision as of 16:53, 11 December 2019

1.90 A resolution structure of Norovirus 3CL protease in complex with the dipeptidyl inhibitor 7l (orthorhombic P form)

Structural highlights

5t6f is a 2 chain structure with sequence from Hu/nv/nv/1968/us. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5t6d, 5t6g
Gene:	ORF1 (Hu/NV/NV/1968/US)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[POLG_NVN68] Protein p48 may play a role in viral replication by interacting with host VAPA, a vesicle-associated membrane protein that plays a role in SNARE-mediated vesicle fusion. This interaction may target replication complex to intracellular membranes.^[1] ^[2] NTPase presumably plays a role in replication. Despite having similarities with helicases, does not seem to display any helicase activity.^[3] ^[4] Protein P22 may play a role in targeting replication complex to intracellular membranes.^[5] ^[6] Viral genome-linked protein is covalently linked to the 5'-end of the positive-strand, negative-strand genomic RNAs and subgenomic RNA. Acts as a genome-linked replication primer. May recruit ribosome to viral RNA thereby promoting viral proteins translation.^[7] ^[8] 3C-like protease processes the polyprotein: 3CLpro-RdRp is first released by autocleavage, then all other proteins are cleaved. May cleave host polyadenylate-binding protein thereby inhibiting cellular translation (By similarity).^[9] ^[10] RNA-directed RNA polymerase replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This sgRNA encodes for structural proteins. Catalyzes the covalent attachment VPg with viral RNAs (By similarity).^[11] ^[12]

Publication Abstract from PubMed

Human noroviruses are the primary cause of epidemic and sporadic acute gastroenteritis. The worldwide high morbidity and mortality associated with norovirus infections, particularly among the elderly, immunocompromised patients and children, constitute a serious public health concern. There are currently no approved human vaccines or norovirus-specific small-molecule therapeutics or prophylactics. Norovirus 3CL protease has recently emerged as a potential therapeutic target for the development of anti-norovirus agents. We hypothesized that the S4 subsite of the enzyme may provide an effective means of designing potent and cell permeable inhibitors of the enzyme. We report herein the structure-guided exploration and exploitation of the S4 subsite of norovirus 3CL protease in the design and synthesis of effective inhibitors of the protease.

Structure-based exploration and exploitation of the S4 subsite of norovirus 3CL protease in the design of potent and permeable inhibitors.,Galasiti Kankanamalage AC, Kim Y, Rathnayake AD, Damalanka VC, Weerawarna PM, Doyle ST, Alsoudi AF, Dissanayake DM, Lushington GH, Mehzabeen N, Battaile KP, Lovell S, Chang KO, Groutas WC Eur J Med Chem. 2016 Nov 14;126:502-516. doi: 10.1016/j.ejmech.2016.11.027. PMID:27914364^[13]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Burroughs JN, Brown F. Presence of a covalently linked protein on calicivirus RNA. J Gen Virol. 1978 Nov;41(2):443-6. PMID:569187
↑ Pfister T, Wimmer E. Polypeptide p41 of a Norwalk-like virus is a nucleic acid-independent nucleoside triphosphatase. J Virol. 2001 Feb;75(4):1611-9. PMID:11160659 doi:10.1128/JVI.75.4.1611-1619.2001
↑ Burroughs JN, Brown F. Presence of a covalently linked protein on calicivirus RNA. J Gen Virol. 1978 Nov;41(2):443-6. PMID:569187
↑ Pfister T, Wimmer E. Polypeptide p41 of a Norwalk-like virus is a nucleic acid-independent nucleoside triphosphatase. J Virol. 2001 Feb;75(4):1611-9. PMID:11160659 doi:10.1128/JVI.75.4.1611-1619.2001
↑ Burroughs JN, Brown F. Presence of a covalently linked protein on calicivirus RNA. J Gen Virol. 1978 Nov;41(2):443-6. PMID:569187
↑ Pfister T, Wimmer E. Polypeptide p41 of a Norwalk-like virus is a nucleic acid-independent nucleoside triphosphatase. J Virol. 2001 Feb;75(4):1611-9. PMID:11160659 doi:10.1128/JVI.75.4.1611-1619.2001
↑ Burroughs JN, Brown F. Presence of a covalently linked protein on calicivirus RNA. J Gen Virol. 1978 Nov;41(2):443-6. PMID:569187
↑ Pfister T, Wimmer E. Polypeptide p41 of a Norwalk-like virus is a nucleic acid-independent nucleoside triphosphatase. J Virol. 2001 Feb;75(4):1611-9. PMID:11160659 doi:10.1128/JVI.75.4.1611-1619.2001
↑ Burroughs JN, Brown F. Presence of a covalently linked protein on calicivirus RNA. J Gen Virol. 1978 Nov;41(2):443-6. PMID:569187
↑ Pfister T, Wimmer E. Polypeptide p41 of a Norwalk-like virus is a nucleic acid-independent nucleoside triphosphatase. J Virol. 2001 Feb;75(4):1611-9. PMID:11160659 doi:10.1128/JVI.75.4.1611-1619.2001
↑ Burroughs JN, Brown F. Presence of a covalently linked protein on calicivirus RNA. J Gen Virol. 1978 Nov;41(2):443-6. PMID:569187
↑ Pfister T, Wimmer E. Polypeptide p41 of a Norwalk-like virus is a nucleic acid-independent nucleoside triphosphatase. J Virol. 2001 Feb;75(4):1611-9. PMID:11160659 doi:10.1128/JVI.75.4.1611-1619.2001
↑ Galasiti Kankanamalage AC, Kim Y, Rathnayake AD, Damalanka VC, Weerawarna PM, Doyle ST, Alsoudi AF, Dissanayake DM, Lushington GH, Mehzabeen N, Battaile KP, Lovell S, Chang KO, Groutas WC. Structure-based exploration and exploitation of the S4 subsite of norovirus 3CL protease in the design of potent and permeable inhibitors. Eur J Med Chem. 2016 Nov 14;126:502-516. doi: 10.1016/j.ejmech.2016.11.027. PMID:27914364 doi:http://dx.doi.org/10.1016/j.ejmech.2016.11.027

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5t6f"

@@ Line 1: / Line 1: @@
 ==1.90 A resolution structure of Norovirus 3CL protease in complex with the dipeptidyl inhibitor 7l (orthorhombic P form)==
-<StructureSection load='5t6f' size='340' side='right' caption='[[5t6f]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='5t6f' size='340' side='right'caption='[[5t6f]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5t6f]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T6F FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5t6f]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hu/nv/nv/1968/us Hu/nv/nv/1968/us]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T6F FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=N38:3-CYCLOHEXYL-N-{(2S)-1-HYDROXY-3-[(3S)-2-OXOPYRROLIDIN-3-YL]PROPAN-2-YL}-N~2~-{[3-(4-METHOXYPHENOXY)PROPYL]SULFONYL}-L-ALANINAMIDE'>N38</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5t6d|5t6d]], [[5t6g|5t6g]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ORF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=524364 Hu/NV/NV/1968/US])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5t6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t6f OCA], [http://pdbe.org/5t6f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t6f RCSB], [http://www.ebi.ac.uk/pdbsum/5t6f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t6f ProSAT]</span></td></tr>
 </table>
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 5t6f" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[SARS Coronavirus Main Proteinase|SARS Coronavirus Main Proteinase]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Hu/nv/nv/1968/us]]
+[[Category: Large Structures]]
 [[Category: Alsoudi, A F]]
 [[Category: Battaile, K P]]

5t6f

From Proteopedia

Revision as of 16:53, 11 December 2019

1.90 A resolution structure of Norovirus 3CL protease in complex with the dipeptidyl inhibitor 7l (orthorhombic P form)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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