3zvf

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{{STRUCTURE_3zvf| PDB=3zvf | SCENE= }}
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==3C protease of Enterovirus 68 complexed with Michael receptor inhibitor 85==
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===3C protease of Enterovirus 68 complexed with Michael receptor inhibitor 85===
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<StructureSection load='3zvf' size='340' side='right' caption='[[3zvf]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23388726}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3zvf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_enterovirus_68 Human enterovirus 68]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZVF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZVF FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=G85:N-[(BENZYLOXY)CARBONYL]-O-TERT-BUTYL-L-SERYL-N-{(2R)-5-ETHOXY-5-OXO-1-[(3S)-2-OXOPYRROLIDIN-3-YL]PENTAN-2-YL}-L-PHENYLALANINAMIDE'>G85</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3zv8|3zv8]], [[3zva|3zva]], [[3zve|3zve]], [[3zvc|3zvc]], [[3zvb|3zvb]], [[3zvg|3zvg]], [[3zv9|3zv9]], [[3zvd|3zvd]]</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Picornain_3C Picornain 3C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.28 3.4.22.28] </span></td></tr>
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<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=3zvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zvf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zvf RCSB], [http://www.ebi.ac.uk/pdbsum/3zvf PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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We have determined the cleavage specificity and the crystal structure of the 3C protease of enterovirus 68 (EV68 3C(pro)). The protease exhibits a typical chymotrypsin fold with a Cys...His...Glu catalytic triad; its three-dimensional structure is closely related to that of the 3C(pro) of rhinovirus 2 as well as to that of poliovirus. The phylogenetic position of the EV68 3C(pro) between the corresponding enzymes of rhinoviruses on the one hand and enteroviruses on the other prompted us to use the crystal structure for the design of irreversible inhibitors, with the goal of discovering broad-spectrum antiviral compounds. We synthesized a series of peptidic alpha,beta-unsaturated ethyl esters of increasing length and for each inhibitor candidate, we determined a crystal structure of its complex with the EV68 3C(pro), which served as the basis for the next design round. To exhibit inhibitory activity, compounds must span at least P3 to P1' ; the most potent inhibitors comprise P4 to P1' . Inhibitory activities were found against the purified 3C protease of EV68 as well as with replicons for poliovirus and EV71 (EC(50) = 0.5 muM for the best compound). Antiviral activities were determined using cell cultures infected with EV71, poliovirus, echovirus 11, and various rhinovirus serotypes. The most potent inhibitor, SG85, exhibited activity with EC(50) values of approximately 180 nM against EV71 and approximately 60 nM against human rhinovirus 14 in a live virus-cell-based assay. Even the shorter SG75, spanning only P3 to P1' , displayed significant activity (EC(50) = 2 to 5 muM) against various rhinoviruses.
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==Function==
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3C protease of enterovirus 68: Structure-based design of Michael acceptor inhibitors and their broad-spectrum antiviral effects against picornaviruses.,Tan J, George S, Kusov Y, Perbandt M, Anemuller S, Mesters JR, Norder H, Coutard B, Lacroix C, Leyssen P, Neyts J, Hilgenfeld R J Virol. 2013 Feb 6. PMID:23388726<ref>PMID:23388726</ref>
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[[http://www.uniprot.org/uniprot/A1E4A3_9ENTO A1E4A3_9ENTO]] Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).[SAAS:SAAS000199_004_016611] Protein 3C is a 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 co-operatively to the protease (By similarity).[SAAS:SAAS000199_004_042266] RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[SAAS:SAAS000199_004_010047]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3zvf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_enterovirus_68 Human enterovirus 68]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZVF OCA].
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</div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Human enterovirus 68]]
[[Category: Human enterovirus 68]]
[[Category: Picornain 3C]]
[[Category: Picornain 3C]]
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[[Category: Hilgenfeld, R.]]
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[[Category: Hilgenfeld, R]]
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[[Category: Mesters, J R.]]
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[[Category: Mesters, J R]]
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[[Category: Perbandt, M.]]
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[[Category: Perbandt, M]]
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[[Category: Tan, J.]]
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[[Category: Tan, J]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Michael inhibitor]]
[[Category: Michael inhibitor]]

Revision as of 09:54, 21 December 2014

3C protease of Enterovirus 68 complexed with Michael receptor inhibitor 85

3zvf, resolution 2.50Å

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