2omx
From Proteopedia
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|PDB= 2omx |SIZE=350|CAPTION= <scene name='initialview01'>2omx</scene>, resolution 1.70Å | |PDB= 2omx |SIZE=350|CAPTION= <scene name='initialview01'>2omx</scene>, resolution 1.70Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= 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]) | |GENE= 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]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1o6s|1O6S]] | ||
| + | |RESOURCES=<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.ebi.ac.uk/pdbsum/2omx PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2omx RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Breast cancer, lobular OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=192090 192090]], Cleft lip with or without cleft palate, with gastric cancer, familial diffuse OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=192090 192090]], Endometrial carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=192090 192090]], Gastric cancer, familial diffuse OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=192090 192090]], Listeria monocytogenes, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=192090 192090]], Ovarian carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=192090 192090]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Schubert, W D.]] | [[Category: Schubert, W D.]] | ||
[[Category: Wollert, T.]] | [[Category: Wollert, T.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: CL]] | ||
[[Category: adhesion protein]] | [[Category: adhesion protein]] | ||
[[Category: cell invasion/cell adhesion complex]] | [[Category: cell invasion/cell adhesion complex]] | ||
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[[Category: leucine-rich-repeat]] | [[Category: leucine-rich-repeat]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:20:07 2008'' |
Revision as of 01:20, 31 March 2008
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| , resolution 1.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | inlA (Listeria monocytogenes), CDH1, CDHE, UVO (Homo sapiens) | ||||||
| Related: | 1O6S
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of InlA S192N G194S+S/hEC1 complex
Overview
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.
About this Structure
2OMX is a Protein complex structure of sequences from Homo sapiens and Listeria monocytogenes. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Mar 31 04:20:07 2008
