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2omx

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Revision as of 09:04, 18 October 2017

Crystal structure of InlA S192N G194S+S/hEC1 complex

Structural highlights

2omx is a 2 chain structure with sequence from Human and Lismo. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1o6s
Gene:	inlA (LISMO), CDH1, CDHE, UVO (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CADH1_HUMAN] Defects in CDH1 are the cause of hereditary diffuse gastric cancer (HDGC) [MIM: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.^[1] ^[2] Defects in CDH1 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:608089]. Defects in CDH1 are a cause of susceptibility to ovarian cancer (OC) [MIM: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

[INLA_LISMO] Mediates the entry of L.monocytogenes into cells. [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.^[3] E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production.^[4]

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 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 < 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.

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^[5]

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

References

↑ Yoon KA, Ku JL, Yang HK, Kim WH, Park SY, Park JG. Germline mutations of E-cadherin gene in Korean familial gastric cancer patients. J Hum Genet. 1999;44(3):177-80. PMID:10319582 doi:10.1007/s100380050137
↑ Yabuta T, Shinmura K, Tani M, Yamaguchi S, Yoshimura K, Katai H, Nakajima T, Mochiki E, Tsujinaka T, Takami M, Hirose K, Yamaguchi A, Takenoshita S, Yokota J. E-cadherin gene variants in gastric cancer families whose probands are diagnosed with diffuse gastric cancer. Int J Cancer. 2002 Oct 10;101(5):434-41. PMID:12216071 doi:10.1002/ijc.10633
↑ Agiostratidou G, Muros RM, Shioi J, Marambaud P, Robakis NK. The cytoplasmic sequence of E-cadherin promotes non-amyloidogenic degradation of A beta precursors. J Neurochem. 2006 Feb;96(4):1182-8. Epub 2006 Jan 26. PMID:16417575 doi:JNC3616
↑ Agiostratidou G, Muros RM, Shioi J, Marambaud P, Robakis NK. The cytoplasmic sequence of E-cadherin promotes non-amyloidogenic degradation of A beta precursors. J Neurochem. 2006 Feb;96(4):1182-8. Epub 2006 Jan 26. PMID:16417575 doi:JNC3616
↑ Wollert T, Heinz DW, Schubert WD. Thermodynamically reengineering the listerial invasion complex InlA/E-cadherin. Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):13960-5. Epub 2007 Aug 22. PMID:17715295

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2omx"

@@ Line 1: / Line 1: @@
 ==Crystal structure of InlA S192N G194S+S/hEC1 complex==
 <StructureSection load='2omx' size='340' side='right' caption='[[2omx]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <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=169963 LISMO]), CDH1, CDHE, UVO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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://pdbe.org/2omx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2omx RCSB], [http://www.ebi.ac.uk/pdbsum/2omx PDBsum]</span></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://pdbe.org/2omx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2omx RCSB], [http://www.ebi.ac.uk/pdbsum/2omx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2omx ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 31: / Line 32: @@
 </div>
 <div class="pdbe-citations 2omx" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Cadherin|Cadherin]]
 == References ==
 <references/>

2omx

From Proteopedia

Revision as of 09:04, 18 October 2017

Crystal structure of InlA S192N G194S+S/hEC1 complex

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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