2xs3: Difference between revisions

Line 1:

[[~~Image~~:~~2xs3~~.~~png~~|~~left~~|~~200px~~]]

==STRUCTURE OF KARILYSIN CATALYTIC MMP DOMAIN==

== Structural highlights ==

<table><tr><td colspan='2'>[[2xs3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Tannerella_forsythia Tannerella forsythia] and [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XS3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XS3 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xs4|2xs4]]</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=2xs3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xs3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xs3 RCSB], [http://www.ebi.ac.uk/pdbsum/2xs3 PDBsum]</span></td></tr>

</table>

== Publication Abstract from PubMed ==

Metallopeptidases (MPs) are among virulence factors secreted by pathogenic bacteria at the site of infection. One such pathogen is Tannerella forsythia, a member of the microbial consortium that causes peridontitis, arguably the most prevalent infective chronic inflammatory disease known to mankind. The only reported MP secreted by T. forsythia is karilysin, a 52 kDa multidomain protein comprising a central 18 kDa catalytic domain (CD), termed Kly18, flanked by domains unrelated to any known protein. We analysed the 3D structure of Kly18 in the absence and presence of Mg(2+) or Ca(2+) , which are required for function and stability, and found that it evidences most of the structural features characteristic of the CDs of mammalian matrix metalloproteinases (MMPs). Unexpectedly, a peptide was bound to the active-site cleft of Kly18 mimicking a left-behind cleavage product, which revealed that the specificity pocket accommodates bulky hydrophobic side-chains of substrates as in mammalian MMPs. In addition, Kly18 displayed a unique Mg(2+) or Ca(2+) binding site and two flexible segments that could play a role in substrate binding. Phylogenetic and sequence similarity studies revealed that Kly18 is evolutionarily much closer to winged-insect and mammalian MMPs than to potential bacterial counterparts found by genomic sequencing projects. Therefore, we conclude that this first structurally characterized non-mammalian MMP is a xenologue co-opted through horizontal gene transfer during the intimate coexistence between T. forsythia and humans or other animals, in a very rare case of gene shuffling from eukaryotes to prokaryotes. Subsequently, this protein would have evolved in a bacterial environment to give rise to full-length karilysin that is furnished with unique flanking domains that do not conform to the general multidomain architecture of animal MMPs.

~~{{STRUCTURE_2xs3| PDB=2xs3 | SCENE= }}~~

The structure of the catalytic domain of Tannerella forsythia karilysin reveals it is a bacterial xenologue of animal matrix metalloproteinases.,Cerda-Costa N, Guevara T, Karim AY, Ksiazek M, Nguyen KA, Arolas JL, Potempa J, Gomis-Ruth FX Mol Microbiol. 2011 Jan;79(1):119-132. doi:, 10.1111/j.1365-2958.2010.07434.x. Epub 2010 Nov 2. PMID:21166898<ref>PMID:21166898</ref>

~~===STRUCTURE OF KARILYSIN CATALYTIC MMP DOMAIN===~~

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

</div>

~~{{ABSTRACT_PUBMED_21166898}}~~

== References ==

~~==About this Structure==~~

__TOC__

~~[[2xs3]] is~~ a ~~4 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Tannerella_forsythia Tannerella forsythia] and [http://en~~.~~wikipedia.org~~/~~wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XS3 OCA].~~

</StructureSection>

==~~Reference~~==

<~~ref group="xtra">PMID:021166898<~~/~~ref><ref group="xtra">PMID:019919176</ref~~><~~ref group="xtra">PMID:020375548</ref><references group="xtra"~~/>

[[Category: Synthetic construct]]

[[Category: Tannerella forsythia]]

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-[[Image:2xs3.png|left|200px]]
+==STRUCTURE OF KARILYSIN CATALYTIC MMP DOMAIN==
+<StructureSection load='2xs3' size='340' side='right' caption='[[2xs3]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2xs3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Tannerella_forsythia Tannerella forsythia] and [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XS3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XS3 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xs4|2xs4]]</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=2xs3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xs3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xs3 RCSB], [http://www.ebi.ac.uk/pdbsum/2xs3 PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Metallopeptidases (MPs) are among virulence factors secreted by pathogenic bacteria at the site of infection. One such pathogen is Tannerella forsythia, a member of the microbial consortium that causes peridontitis, arguably the most prevalent infective chronic inflammatory disease known to mankind. The only reported MP secreted by T. forsythia is karilysin, a 52 kDa multidomain protein comprising a central 18 kDa catalytic domain (CD), termed Kly18, flanked by domains unrelated to any known protein. We analysed the 3D structure of Kly18 in the absence and presence of Mg(2+) or Ca(2+) , which are required for function and stability, and found that it evidences most of the structural features characteristic of the CDs of mammalian matrix metalloproteinases (MMPs). Unexpectedly, a peptide was bound to the active-site cleft of Kly18 mimicking a left-behind cleavage product, which revealed that the specificity pocket accommodates bulky hydrophobic side-chains of substrates as in mammalian MMPs. In addition, Kly18 displayed a unique Mg(2+) or Ca(2+) binding site and two flexible segments that could play a role in substrate binding. Phylogenetic and sequence similarity studies revealed that Kly18 is evolutionarily much closer to winged-insect and mammalian MMPs than to potential bacterial counterparts found by genomic sequencing projects. Therefore, we conclude that this first structurally characterized non-mammalian MMP is a xenologue co-opted through horizontal gene transfer during the intimate coexistence between T. forsythia and humans or other animals, in a very rare case of gene shuffling from eukaryotes to prokaryotes. Subsequently, this protein would have evolved in a bacterial environment to give rise to full-length karilysin that is furnished with unique flanking domains that do not conform to the general multidomain architecture of animal MMPs.
-{{STRUCTURE_2xs3|  PDB=2xs3  |  SCENE=  }}
+The structure of the catalytic domain of Tannerella forsythia karilysin reveals it is a bacterial xenologue of animal matrix metalloproteinases.,Cerda-Costa N, Guevara T, Karim AY, Ksiazek M, Nguyen KA, Arolas JL, Potempa J, Gomis-Ruth FX Mol Microbiol. 2011 Jan;79(1):119-132. doi:, 10.1111/j.1365-2958.2010.07434.x. Epub 2010 Nov 2. PMID:21166898<ref>PMID:21166898</ref>
-===STRUCTURE OF KARILYSIN CATALYTIC MMP DOMAIN===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_21166898}}
+== References ==
+<references/>
-==About this Structure==
+__TOC__
-[[2xs3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Tannerella_forsythia Tannerella forsythia] and [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XS3 OCA].
+</StructureSection>
-==Reference==
-<ref group="xtra">PMID:021166898</ref><ref group="xtra">PMID:019919176</ref><ref group="xtra">PMID:020375548</ref><references group="xtra"/>
 [[Category: Synthetic construct]]
 [[Category: Tannerella forsythia]]