2h9h: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image: | ==An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors== | ||
<StructureSection load='2h9h' size='340' side='right' caption='[[2h9h]], [[Resolution|resolution]] 1.39Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2h9h]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_a_virus Hepatitis a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H9H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2H9H FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BBL:N-[(BENZYLOXY)CARBONYL]-L-ALANINE'>BBL</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=QMM:N,N-DIMETHYL-L-GLUTAMINE'>QMM</scene></td></tr> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2a4o|2a4o]], [[2cxv|2cxv]], [[1hav|1hav]], [[1qa7|1qa7]], [[2h6m|2h6m]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">3C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12092 Hepatitis A virus])</td></tr> | |||
<tr><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> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2h9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h9h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2h9h RCSB], [http://www.ebi.ac.uk/pdbsum/2h9h PDBsum]</span></td></tr> | |||
<table> | |||
== 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/h9/2h9h_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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We have solved the crystal and molecular structures of hepatitis A viral (HAV) 3C proteinase, a cysteine peptidase having a chymotrypsin-like protein fold, in complex with each of three tetrapeptidyl-based methyl ketone inhibitors to resolutions beyond 1.4 A, the highest resolution to date for a 3C or a 3C-Like (e.g. SARS viral main proteinase) peptidase. The residues of the beta-hairpin motif (residues 138-158), an extension of two beta-strands of the C-terminal beta-barrel of HAV 3C are critical for the interactions between the enzyme and the tetrapeptide portion of these inhibitors that are analogous to the residues at the P4 to P1 positions in the natural substrates of picornaviral 3C proteinases. Unexpectedly, the Sgamma of Cys172 forms two covalent bonds with each inhibitor, yielding an unusual episulfide cation (thiiranium ring) stabilized by a nearby oxyanion. This result suggests a mechanism of inactivation of 3C peptidases by methyl ketone inhibitors that is distinct from that occurring in the structurally related serine proteinases or in the papain-like cysteine peptidases. It also provides insight into the mechanisms underlying both the inactivation of HAV 3C by these inhibitors and on the proteolysis of natural substrates by this viral cysteine peptidase. | |||
An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors.,Yin J, Cherney MM, Bergmann EM, Zhang J, Huitema C, Pettersson H, Eltis LD, Vederas JC, James MN J Mol Biol. 2006 Aug 25;361(4):673-86. Epub 2006 Jul 7. PMID:16860823<ref>PMID:16860823</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Virus protease|Virus protease]] | *[[Virus protease|Virus protease]] | ||
*[[3C protease|3C protease]] | |||
== | == References == | ||
< | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Hepatitis a virus]] | [[Category: Hepatitis a virus]] | ||
[[Category: Picornain 3C]] | [[Category: Picornain 3C]] | ||
Revision as of 07:33, 29 September 2014
An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitorsAn episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe have solved the crystal and molecular structures of hepatitis A viral (HAV) 3C proteinase, a cysteine peptidase having a chymotrypsin-like protein fold, in complex with each of three tetrapeptidyl-based methyl ketone inhibitors to resolutions beyond 1.4 A, the highest resolution to date for a 3C or a 3C-Like (e.g. SARS viral main proteinase) peptidase. The residues of the beta-hairpin motif (residues 138-158), an extension of two beta-strands of the C-terminal beta-barrel of HAV 3C are critical for the interactions between the enzyme and the tetrapeptide portion of these inhibitors that are analogous to the residues at the P4 to P1 positions in the natural substrates of picornaviral 3C proteinases. Unexpectedly, the Sgamma of Cys172 forms two covalent bonds with each inhibitor, yielding an unusual episulfide cation (thiiranium ring) stabilized by a nearby oxyanion. This result suggests a mechanism of inactivation of 3C peptidases by methyl ketone inhibitors that is distinct from that occurring in the structurally related serine proteinases or in the papain-like cysteine peptidases. It also provides insight into the mechanisms underlying both the inactivation of HAV 3C by these inhibitors and on the proteolysis of natural substrates by this viral cysteine peptidase. An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors.,Yin J, Cherney MM, Bergmann EM, Zhang J, Huitema C, Pettersson H, Eltis LD, Vederas JC, James MN J Mol Biol. 2006 Aug 25;361(4):673-86. Epub 2006 Jul 7. PMID:16860823[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||||||