2dg3
From Proteopedia
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| - | [[Image:2dg3.gif|left|200px]] | + | [[Image:2dg3.gif|left|200px]] |
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| - | '''Wildtype FK506-binding protein complexed with Rapamycin''' | + | {{Structure |
| + | |PDB= 2dg3 |SIZE=350|CAPTION= <scene name='initialview01'>2dg3</scene>, resolution 1.70Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=RAP:RAPAMYCIN+IMMUNOSUPPRESSANT+DRUG'>RAP</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Wildtype FK506-binding protein complexed with Rapamycin''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2DG3 is a [ | + | 2DG3 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DG3 OCA]. |
==Reference== | ==Reference== | ||
| - | Energetic and structural analysis of the role of tryptophan 59 in FKBP12., Fulton KF, Jackson SE, Buckle AM, Biochemistry. 2003 Mar 4;42(8):2364-72. PMID:[http:// | + | Energetic and structural analysis of the role of tryptophan 59 in FKBP12., Fulton KF, Jackson SE, Buckle AM, Biochemistry. 2003 Mar 4;42(8):2364-72. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12600203 12600203] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Peptidylprolyl isomerase]] | [[Category: Peptidylprolyl isomerase]] | ||
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[[Category: rotamase]] | [[Category: rotamase]] | ||
| - | ''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 16:26:57 2008'' |
Revision as of 14:26, 20 March 2008
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| , resolution 1.70Å | |||||||
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| Ligands: | and | ||||||
| Activity: | Peptidylprolyl isomerase, with EC number 5.2.1.8 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Wildtype FK506-binding protein complexed with Rapamycin
Overview
Tryptophan 59 forms the seat of the hydrophobic ligand-binding site in the small immunophilin FKBP12. Mutating this residue to phenylalanine or leucine stabilizes the protein by 2.72 and 2.35 kcal mol(-1), respectively. Here we report the stability data and 1.7 A resolution crystal structures of both mutant proteins, complexed with the immunosuppressant rapamycin. Both structures show a relatively large response to mutation involving a helical bulge at the mutation site and the loss of a hydrogen bond that anchors a nearby loop. The increased stability of the mutants is probably due to a combination of improved packing and an entropic gain at the mutation site. The structures are almost identical to that of wild-type FKBP12.6, an isoform of FKBP12 that differs by 18 residues, including Trp59, in its sequence. Therefore, the structural difference between the two isoforms can be attributed almost entirely to the identity of residue 59. It is likely that in FKBP12-ligand complexes Trp59 provides added binding energy at the active site at the expense of protein stability, a characteristic common to other proteins. FKBP12 associates with the ryanodine receptor in skeletal muscle (RyR1), while FKBP12.6 selectively binds the ryanodine receptor in cardiac muscle (RyR2). The structural response to mutation suggests that residue 59 contributes to the specificity of binding between FKBP12 isoforms and ryanodine receptors.
About this Structure
2DG3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Energetic and structural analysis of the role of tryptophan 59 in FKBP12., Fulton KF, Jackson SE, Buckle AM, Biochemistry. 2003 Mar 4;42(8):2364-72. PMID:12600203
Page seeded by OCA on Thu Mar 20 16:26:57 2008
