1y4c
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1y4c.gif|left|200px]] | + | [[Image:1y4c.gif|left|200px]] |
| - | + | ||
| - | '''Designed Helical Protein fusion MBP''' | + | {{Structure |
| + | |PDB= 1y4c |SIZE=350|CAPTION= <scene name='initialview01'>1y4c</scene>, resolution 1.900Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= | ||
| + | |GENE= malE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]) | ||
| + | }} | ||
| + | |||
| + | '''Designed Helical Protein fusion MBP''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1Y4C is a [ | + | 1Y4C is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y4C OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15684085 15684085] |
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 22: | Line 31: | ||
[[Category: maltose binding protein fusion]] | [[Category: maltose binding protein fusion]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:18:15 2008'' |
Revision as of 13:18, 20 March 2008
| |||||||
| , resolution 1.900Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | malE (Escherichia coli) | ||||||
| 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
Page seeded by OCA on Thu Mar 20 15:18:15 2008
