View source for 1qmy


==FMDV LEADER PROTEASE (LBSHORT-C51A-C133S)==
<StructureSection load='1qmy' size='340' side='right'caption='[[1qmy]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1qmy]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Foot-and-mouth_disease_virus_O Foot-and-mouth disease virus O]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QMY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QMY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=1qmy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qmy OCA], [https://pdbe.org/1qmy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qmy RCSB], [https://www.ebi.ac.uk/pdbsum/1qmy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qmy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/POLG_FMDVO POLG_FMDVO] The leader protease autocatalytically cleaves itself from the polyprotein at the L/VP0 junction. It also cleaves the host translation initiation factor EIF4G1 and EIF4G3, in order to shut down the capped cellular mRNA transcription.<ref>PMID:8386879</ref> <ref>PMID:11034318</ref> <ref>PMID:15016848</ref> <ref>PMID:18614639</ref>   Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with host heparan sulfate and various integrins (alphavbeta6, alphavbeta1, alphavbeta3, alpha5beta1, alphavbeta8) to provide virion attachment to target Attachment via host integrins induces virion internalization predominantly through clathrin-mediated endocytosis. In strains adapted to cell culture, attachment to heparan sulfate can also be used and induces virion internalization through clathrin- and caveolin-independent endocytosis.<ref>PMID:8386879</ref> <ref>PMID:11034318</ref> <ref>PMID:15016848</ref> <ref>PMID:18614639</ref>   Protein VP0: VP0 precursor is a component of immature procapsids (By similarity).<ref>PMID:8386879</ref> <ref>PMID:11034318</ref> <ref>PMID:15016848</ref> <ref>PMID:18614639</ref>   Protein 2B: Affects membrane integrity and cause an increase in membrane permeability (By similarity).<ref>PMID:8386879</ref> <ref>PMID:11034318</ref> <ref>PMID:15016848</ref> <ref>PMID:18614639</ref>   Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).<ref>PMID:8386879</ref> <ref>PMID:11034318</ref> <ref>PMID:15016848</ref> <ref>PMID:18614639</ref>   Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity).<ref>PMID:8386879</ref> <ref>PMID:11034318</ref> <ref>PMID:15016848</ref> <ref>PMID:18614639</ref>   Protein 3B-1, 3B-2 and 3B-3 are covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. They acts as a genome-linked replication primer (By similarity).<ref>PMID:8386879</ref> <ref>PMID:11034318</ref> <ref>PMID:15016848</ref> <ref>PMID:18614639</ref>   Protease 3C: cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease (By similarity).<ref>PMID:8386879</ref> <ref>PMID:11034318</ref> <ref>PMID:15016848</ref> <ref>PMID:18614639</ref>   RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).<ref>PMID:8386879</ref> <ref>PMID:11034318</ref> <ref>PMID:15016848</ref> <ref>PMID:18614639</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qm/1qmy_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1qmy ConSurf].
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== Publication Abstract from PubMed ==
The structures of the two leader protease (Lpro) variants of foot-and-mouth disease virus known to date were solved using crystals in which molecules were organized as molecular fibers. Such crystals diffract to a resolution of only approximately 3 A. This singular, pseudo-polymeric organization is present in a new Lpro crystal form showing a cubic packing. As molecular fiber formation appeared unrelated to crystallization conditions, we mutated the reactive cysteine 133 residue, which makes a disulfide bridge between adjacent monomers in the fibers, to serine. None of the intermolecular contacts found in the molecular fibers was present in crystals of this variant. Analysis of this Lpro structure, refined at 1.9 A resolution, enables a detailed definition of the active center of the enzyme, including the solvent organization. Assay of Lpro activity on a fluorescent hexapeptide substrate showed that Lpro, in contrast to papain, was highly sensitive to increases in the cation concentration and was active only across a narrow pH range. Examination of the Lpro structure revealed that three aspartate residues near the active site, not present in papain-like enzymes, are probably responsible for these properties.

Structural and biochemical features distinguish the foot-and-mouth disease virus leader proteinase from other papain-like enzymes.,Guarne A, Hampoelz B, Glaser W, Carpena X, Tormo J, Fita I, Skern T J Mol Biol. 2000 Oct 6;302(5):1227-40. PMID:11183785<ref>PMID:11183785</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1qmy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Virus protease 3D structures|Virus protease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Foot-and-mouth disease virus O]]
[[Category: Large Structures]]
[[Category: Fita I]]
[[Category: Glaser W]]
[[Category: Guarne A]]
[[Category: Skern T]]
[[Category: Tormo J]]