This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

6nu9

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Crystal Structure of a Zinc-Binding Non-Structural Protein from the Hepatitis E Virus

Structural highlights

6nu9 is a 1 chain structure with sequence from Orthohepevirus A. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.761Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

POLN_HEVPA Methyltransferase: Displays a capping enzyme activity. This function is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus. The enzymatic reaction involves a covalent link between 7-methyl-GMP and the methyltransferase, whereas eukaryotic capping enzymes form a covalent complex only with GMP. Methyltransferase catalyzes transfer of a methyl group from S-adenosylmethionine to GTP and GDP to yield m(7)GTP or m(7)GDP. GDP is a better substrate than GTP. This enzyme also displays guanylyltransferase activity to form a covalent complex, methyltransferase-m(7)GMP, from which 7-methyl-GMP is transferred to the mRNA to create the cap structure.[UniProtKB:Q81862] Y-domain: Indispensable for virus replication.[UniProtKB:Q81862] Putative protease: May participate in the processing of polyprotein pORF1 and capsid protein ORF2, possibly together with cellular proteases. Inhibits induction of IFN-beta by MDA5 and RIG-I pathways and down-regulates the expression of MDA5.[UniProtKB:Q81862] NTPase/helicase: Multi-functional protein that exhibits NTPase and RNA unwinding activities (By similarity). Hydrolyzes all NTPs efficiently and unwinds RNA duplexes containing 5' overhangs (By similarity). Possesses a sequence independent RNA-5'-triphosphatase (RTPase) activity suggestive of its role in forming viral cap structure. Participates also in viral genome replication, RNA translocation and genome packaging/unpackaging (By similarity).[UniProtKB:P29324][UniProtKB:Q81862] RNA-directed RNA polymerase: Plays an essential role in the virus replication (By similarity). Binds to the 3'-end of the genomic RNA to initiate viral replication (By similarity).[UniProtKB:Q81862][UniProtKB:Q9WC28]

1 Structural highlights
2 Function

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6nu9"

Categories: Large Structures | Orthohepevirus A | Bussiere D | Proudfoot A

@@ Line 3: / Line 3: @@
 <StructureSection load='6nu9' size='340' side='right'caption='[[6nu9]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6nu9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Hev Hev]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NU9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NU9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6nu9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Orthohepevirus_A Orthohepevirus A]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NU9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NU9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO2:NITRITE+ION'>NO2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.761&#8491;</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=6nu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nu9 OCA], [http://pdbe.org/6nu9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nu9 RCSB], [http://www.ebi.ac.uk/pdbsum/6nu9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nu9 ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO2:NITRITE+ION'>NO2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6nu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nu9 OCA], [https://pdbe.org/6nu9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nu9 RCSB], [https://www.ebi.ac.uk/pdbsum/6nu9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nu9 ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[https://www.uniprot.org/uniprot/POLN_HEVPA POLN_HEVPA] Methyltransferase: Displays a capping enzyme activity. This function is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus. The enzymatic reaction involves a covalent link between 7-methyl-GMP and the methyltransferase, whereas eukaryotic capping enzymes form a covalent complex only with GMP. Methyltransferase catalyzes transfer of a methyl group from S-adenosylmethionine to GTP and GDP to yield m(7)GTP or m(7)GDP. GDP is a better substrate than GTP. This enzyme also displays guanylyltransferase activity to form a covalent complex, methyltransferase-m(7)GMP, from which 7-methyl-GMP is transferred to the mRNA to create the cap structure.[UniProtKB:Q81862]  Y-domain: Indispensable for virus replication.[UniProtKB:Q81862]  Putative protease: May participate in the processing of polyprotein pORF1 and capsid protein ORF2, possibly together with cellular proteases. Inhibits induction of IFN-beta by MDA5 and RIG-I pathways and down-regulates the expression of MDA5.[UniProtKB:Q81862]  NTPase/helicase: Multi-functional protein that exhibits NTPase and RNA unwinding activities (By similarity). Hydrolyzes all NTPs efficiently and unwinds RNA duplexes containing 5' overhangs (By similarity). Possesses a sequence independent RNA-5'-triphosphatase (RTPase) activity suggestive of its role in forming viral cap structure. Participates also in viral genome replication, RNA translocation and genome packaging/unpackaging (By similarity).[UniProtKB:P29324][UniProtKB:Q81862]  RNA-directed RNA polymerase: Plays an essential role in the virus replication (By similarity). Binds to the 3'-end of the genomic RNA to initiate viral replication (By similarity).[UniProtKB:Q81862][UniProtKB:Q9WC28]
-Hepatitis E virus (HEV) is a 7.2 kb positive-sense, single-stranded RNA virus containing three partially overlapping reading frames, ORF 1-3. All non-structural proteins required for viral replication are encoded by ORF1 and are transcribed as a single transcript. Computational analysis of the complete ORF1 polyprotein identified a previously uncharacterized region of predicted secondary structure bordered by two disordered regions coinciding partially with a region predicted as a putative cysteine protease. Following successful cloning, expression and purification of this region, the crystal structure of the identified protein was determined and identified to have considerable structural homology to a fatty acid binding domain. Further analysis of the structure revealed a metal binding site, shown unambiguously to specifically bind zinc via a non-classical, potentially catalytic zinc-binding motif. Based on the structural homology of the HEV protein with known structures, along with the presence of a catalytic zinc-binding motif, it is possible that the identified protein corresponds to the HEV protease, which could require activation or repression through the binding of a fatty acid. This represents a significant step forward in the characterization and the understanding of the molecular mechanisms of the HEV genome. We present analysis for the first time of this identified non-structural protein, expanding the knowledge and understanding of the complex mechanisms of HEV biology.IMPORTANCE Hepatitis E virus (HEV) is an emerging virus found predominately in developing countries causing an estimated 20 million infections, which result in approximately 57,000 deaths a year. Although it is known that the non-structural proteins of the HEV ORF1 are expressed as a single transcript, there is debate as to whether ORF1 functions as a single polyprotein or if it is processed into separate domains via a viral or endogenous cellular protease. In the following paper, we present the first structural and biophysical characterization of a HEV non-structural protein using a construct that has partially overlapping boundaries with the predicted putative cysteine protease.
-First Crystal Structure of a Non-Structural Hepatitis E Viral Protein Identifies a Putative Novel Zinc-Binding Protein.,Proudfoot A, Hyrina A, Holdorf M, Frank AO, Bussiere D J Virol. 2019 Apr 24. pii: JVI.00170-19. doi: 10.1128/JVI.00170-19. PMID:31019049<ref>PMID:31019049</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 6nu9" style="background-color:#fffaf0;"></div>
-== References ==
-<references/>
 __TOC__
 </StructureSection>
-[[Category: Hev]]
 [[Category: Large Structures]]
-[[Category: Bussiere, D]]
+[[Category: Orthohepevirus A]]
-[[Category: Proudfoot, A]]
+[[Category: Bussiere D]]
-[[Category: Non-structural protein]]
+[[Category: Proudfoot A]]
-[[Category: Viral protein]]
-[[Category: Zinc-binding]]

6nu9

From Proteopedia

Current revision

Crystal Structure of a Zinc-Binding Non-Structural Protein from the Hepatitis E Virus

Structural highlights

Function

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox