1y4c
From Proteopedia
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|PDB= 1y4c |SIZE=350|CAPTION= <scene name='initialview01'>1y4c</scene>, resolution 1.900Å | |PDB= 1y4c |SIZE=350|CAPTION= <scene name='initialview01'>1y4c</scene>, resolution 1.900Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=GLC:GLUCOSE'>GLC</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= malE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]) | |GENE= malE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[4hb1|4HB1]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1y4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y4c OCA], [http://www.ebi.ac.uk/pdbsum/1y4c PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1y4c RCSB]</span> | ||
}} | }} | ||
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[[Category: maltose binding protein fusion]] | [[Category: maltose binding protein fusion]] | ||
| - | ''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 00:58:35 2008'' |
Revision as of 21:58, 30 March 2008
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| , resolution 1.900Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | malE (Escherichia coli) | ||||||
| Related: | 4HB1
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Designed Helical Protein fusion MBP
Overview
An IL-4 antagonist was designed based on structural and biochemical analysis of unbound IL-4 and IL-4 in complex with its high-affinity receptor (IL-4Ralpha). Our design strategy sought to capture a protein-protein interaction targeting the high affinity that IL-4 has for IL-4Ralpha. This strategy has impact due to the potential relevance of IL-4Ralpha as a drug target in the treatment of asthma. To mimic the IL-4 binding surface, critical side chains for receptor binding were identified, and these side chains were transplanted onto a previously characterized, de novo-designed four-helix protein called designed helical protein 1 (DHP-1). This first-generation design resolved the ambiguity previously described for the connectivity between helices in DHP-1 and resulted in a protein capable of binding to IL-4Ralpha. The second-generation antagonist was based upon further molecular modeling, and it succeeded in binding IL-4Ralpha better than the first-generation. This protein, termed DHP-14-AB, yielded a protein with a cooperative unfolding transition (DeltaGu0=8.1 kcal/mol) and an IC50 of 27 microM when in competition with IL-4 whereas DHP-1 had no affinity for IL-4Ralpha. The crystal structure of DHP-14-AB was determined to 1.9-A resolution and was compared with IL-4. This comparison revealed how design strategies targeting protein-protein interactions require high-resolution 3D data and the incorporation of orientation-specific information at the level of side-chains and secondary structure element interactions.
About this Structure
1Y4C is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
De novo design of an IL-4 antagonist and its structure at 1.9 A., Laporte SL, Forsyth CM, Cunningham BC, Miercke LJ, Akhavan D, Stroud RM, Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1889-94. Epub 2005 Jan 31. PMID:15684085
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