1cwb: Difference between revisions
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[[Image:1cwb.gif|left|200px]] | [[Image:1cwb.gif|left|200px]] | ||
'''THE X-RAY STRUCTURE OF (MEBM2T)1-CYCLOSPORIN COMPLEXED WITH CYCLOPHILIN A PROVIDES AN EXPLANATION FOR ITS ANOMALOUSLY HIGH IMMUNOSUPPRESSIVE ACTIVITY''' | {{Structure | ||
|PDB= 1cwb |SIZE=350|CAPTION= <scene name='initialview01'>1cwb</scene>, resolution 2.2Å | |||
|SITE= | |||
|LIGAND= | |||
|ACTIVITY= | |||
|GENE= CYCLOPHILIN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''THE X-RAY STRUCTURE OF (MEBM2T)1-CYCLOSPORIN COMPLEXED WITH CYCLOPHILIN A PROVIDES AN EXPLANATION FOR ITS ANOMALOUSLY HIGH IMMUNOSUPPRESSIVE ACTIVITY''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1CWB is a [ | 1CWB 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=1CWB OCA]. | ||
==Reference== | ==Reference== | ||
The X-ray structure of (MeBm2t)1-cyclosporin complexed with cyclophilin A provides an explanation for its anomalously high immunosuppressive activity., Mikol V, Kallen J, Walkinshaw MD, Protein Eng. 1994 May;7(5):597-603. PMID:[http:// | The X-ray structure of (MeBm2t)1-cyclosporin complexed with cyclophilin A provides an explanation for its anomalously high immunosuppressive activity., Mikol V, Kallen J, Walkinshaw MD, Protein Eng. 1994 May;7(5):597-603. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8073029 8073029] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: complex (isomerase/immunosuppressant)]] | [[Category: complex (isomerase/immunosuppressant)]] | ||
''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 10:29:47 2008'' | ||
Revision as of 11:29, 20 March 2008
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| , resolution 2.2Å | |||||||
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| Gene: | CYCLOPHILIN (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
THE X-RAY STRUCTURE OF (MEBM2T)1-CYCLOSPORIN COMPLEXED WITH CYCLOPHILIN A PROVIDES AN EXPLANATION FOR ITS ANOMALOUSLY HIGH IMMUNOSUPPRESSIVE ACTIVITY
OverviewOverview
For most of the cyclosporin A (CsA) analogs, there is generally a good correlation between cyclophilin binding and immunosuppression. However, this relationship does not seem to hold for 4-[(E)-2-butenyl]-4,4,N-trimethyl-L-threonine1 (MeBm2t)1-CsA. Its affinity for cyclophilin was reported to be approximately 1% that of CsA and its immunosuppressive activity in vitro was shown to be approximately 30% that of CsA. We report here the crystal structure of a complex between recombinant human cyclophilin A (CypA) and (MeBm2t)1-CsA which has been determined by X-ray crystallography at 2.2 A resolution and refined to an R-factor of 16.3%. (MeBm2t)1-CsA shows a similar bound conformation and network of interactions to CypA as CsA. The measured lower affinity for CypA cannot therefore be explained by a different mode of binding. We propose that the poor affinity to CypA could be accounted for by the existence of an equilibrium in aqueous solution between a 'cyclophilin bound conformation' and a 'non-binding conformation' of (MeBm2t)1-CsA. The relatively high immunosuppressive activity is suggested to result from slight conformational differences observed in the effector domain.
About this StructureAbout this Structure
1CWB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The X-ray structure of (MeBm2t)1-cyclosporin complexed with cyclophilin A provides an explanation for its anomalously high immunosuppressive activity., Mikol V, Kallen J, Walkinshaw MD, Protein Eng. 1994 May;7(5):597-603. PMID:8073029
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