1bl4

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[[Image:1bl4.gif|left|200px]]
[[Image:1bl4.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1bl4 |SIZE=350|CAPTION= <scene name='initialview01'>1bl4</scene>, resolution 1.9&Aring;
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The line below this paragraph, containing "STRUCTURE_1bl4", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=AP1:{3-[3-(3,4-DIMETHOXY-PHENYL)-1-(1-{1-[2-(3,4,5-TRIMETHOXY-PHENYL)-BUTYRYL]-PIPERIDIN-2YL}-VINYLOXY)-PROPYL]-PHENOXY}-ACETIC+ACID'>AP1</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_1bl4| PDB=1bl4 | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bl4 OCA], [http://www.ebi.ac.uk/pdbsum/1bl4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1bl4 RCSB]</span>
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}}
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'''FKBP MUTANT F36V COMPLEXED WITH REMODELED SYNTHETIC LIGAND'''
'''FKBP MUTANT F36V COMPLEXED WITH REMODELED SYNTHETIC LIGAND'''
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[[Category: Wood, S A.]]
[[Category: Wood, S A.]]
[[Category: Yang, W.]]
[[Category: Yang, W.]]
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[[Category: isomerase]]
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[[Category: Isomerase]]
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[[Category: rotamase]]
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[[Category: Rotamase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:39:18 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:03:17 2008''
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Revision as of 08:39, 2 May 2008

Image:1bl4.gif

Template:STRUCTURE 1bl4

FKBP MUTANT F36V COMPLEXED WITH REMODELED SYNTHETIC LIGAND


Overview

FKBP ligand homodimers can be used to activate signaling events inside cells and animals that have been engineered to express fusions between appropriate signaling domains and FKBP. However, use of these dimerizers in vivo is potentially limited by ligand binding to endogenous FKBP. We have designed ligands that bind specifically to a mutated FKBP over the wild-type protein by remodeling an FKBP-ligand interface to introduce a specificity binding pocket. A compound bearing an ethyl substituent in place of a carbonyl group exhibited sub-nanomolar affinity and 1,000-fold selectivity for a mutant FKBP with a compensating truncation of a phenylalanine residue. Structural and functional analysis of the new pocket showed that recognition is surprisingly relaxed, with the modified ligand only partially filling the engineered cavity. We incorporated the specificity pocket into a fusion protein containing FKBP and the intracellular domain of the Fas receptor. Cells expressing this modified chimeric protein potently underwent apoptosis in response to AP1903, a homodimer of the modified ligand, both in culture and when implanted into mice. Remodeled dimerizers such as AP1903 are ideal reagents for controlling the activities of cells that have been modified by gene therapy procedures, without interference from endogenous FKBP.

About this Structure

1BL4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity., Clackson T, Yang W, Rozamus LW, Hatada M, Amara JF, Rollins CT, Stevenson LF, Magari SR, Wood SA, Courage NL, Lu X, Cerasoli F Jr, Gilman M, Holt DA, Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10437-42. PMID:9724721 Page seeded by OCA on Fri May 2 11:39:18 2008

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