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{{STRUCTURE_2omx| PDB=2omx |  SCENE=  }}
==Crystal structure of InlA S192N G194S+S/hEC1 complex==
===Crystal structure of InlA S192N G194S+S/hEC1 complex===
<StructureSection load='2omx' size='340' side='right' caption='[[2omx]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
{{ABSTRACT_PUBMED_17715295}}
== Structural highlights ==
<table><tr><td colspan='2'>[[2omx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Listeria_monocytogenes Listeria monocytogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OMX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2OMX FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1o6s|1o6s]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">inlA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1639 Listeria monocytogenes]), CDH1, CDHE, UVO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=2omx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2omx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2omx RCSB], [http://www.ebi.ac.uk/pdbsum/2omx PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/CADH1_HUMAN CADH1_HUMAN]] Defects in CDH1 are the cause of hereditary diffuse gastric cancer (HDGC) [MIM:[http://omim.org/entry/137215 137215]]. An autosomal dominant cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. Note=Heterozygous germline mutations CDH1 are responsible for familial cases of diffuse gastric cancer. Somatic mutations in the has also been found in patients with sporadic diffuse gastric cancer and lobular breast cancer.<ref>PMID:10319582</ref> <ref>PMID:12216071</ref>  Defects in CDH1 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[http://omim.org/entry/608089 608089]]. Defects in CDH1 are a cause of susceptibility to ovarian cancer (OC) [MIM:[http://omim.org/entry/167000 167000]]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.
== Function ==
[[http://www.uniprot.org/uniprot/INLA_LISMO INLA_LISMO]] Mediates the entry of L.monocytogenes into cells. [[http://www.uniprot.org/uniprot/CADH1_HUMAN CADH1_HUMAN]] Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells. Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7.<ref>PMID:16417575</ref>  E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production.<ref>PMID:16417575</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/om/2omx_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 ==
Biological processes essentially all depend on the specific recognition between macromolecules and their interaction partners. Although many such interactions have been characterized both structurally and biophysically, the thermodynamic effects of small atomic changes remain poorly understood. Based on the crystal structure of the bacterial invasion protein internalin (InlA) of Listeria monocytogenes in complex with its human receptor E-cadherin (hEC1), we analyzed the interface to identify single amino acid substitutions in InlA that would potentially improve the overall quality of interaction and hence increase the weak binding affinity of the complex. Dissociation constants of InlA-variant/hEC1 complexes, as well as enthalpy and entropy of binding, were quantified by isothermal titration calorimetry. All single substitutions indeed significantly increase binding affinity. Structural changes were verified crystallographically at &lt; or =2.0-A resolution, allowing thermodynamic characteristics of single substitutions to be rationalized structurally and providing unique insights into atomic contributions to binding enthalpy and entropy. Structural and thermodynamic data of all combinations of individual substitutions result in a thermodynamic network, allowing the source of cooperativity between distant recognition sites to be identified. One such pair of single substitutions improves affinity 5,000-fold. We thus demonstrate that rational reengineering of protein complexes is possible by making use of physically distant hot spots of recognition.


==Disease==
Thermodynamically reengineering the listerial invasion complex InlA/E-cadherin.,Wollert T, Heinz DW, Schubert WD Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):13960-5. Epub 2007 Aug 22. PMID:17715295<ref>PMID:17715295</ref>
[[http://www.uniprot.org/uniprot/CADH1_HUMAN CADH1_HUMAN]] Defects in CDH1 are the cause of hereditary diffuse gastric cancer (HDGC) [MIM:[http://omim.org/entry/137215 137215]]. An autosomal dominant cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. Note=Heterozygous germline mutations CDH1 are responsible for familial cases of diffuse gastric cancer. Somatic mutations in the has also been found in patients with sporadic diffuse gastric cancer and lobular breast cancer.<ref>PMID:10319582</ref><ref>PMID:12216071</ref> Defects in CDH1 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[http://omim.org/entry/608089 608089]].  Defects in CDH1 are a cause of susceptibility to ovarian cancer (OC) [MIM:[http://omim.org/entry/167000 167000]]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.


==Function==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[http://www.uniprot.org/uniprot/INLA_LISMO INLA_LISMO]] Mediates the entry of L.monocytogenes into cells. [[http://www.uniprot.org/uniprot/CADH1_HUMAN CADH1_HUMAN]] Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells. Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7.<ref>PMID:16417575</ref>  E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production.<ref>PMID:16417575</ref>  
</div>
 
==About this Structure==
[[2omx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Listeria_monocytogenes Listeria monocytogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OMX OCA].


==See Also==
==See Also==
*[[Cadherin|Cadherin]]
*[[Cadherin|Cadherin]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:017715295</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Listeria monocytogenes]]
[[Category: Listeria monocytogenes]]
[[Category: Heinz, D W.]]
[[Category: Heinz, D W]]
[[Category: Schubert, W D.]]
[[Category: Schubert, W D]]
[[Category: Wollert, T.]]
[[Category: Wollert, T]]
[[Category: Adhesion protein]]
[[Category: Adhesion protein]]
[[Category: Cell invasion-cell adhesion complex]]
[[Category: Cell invasion-cell adhesion complex]]

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