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< | ==THE MUTANT E.COLI F112W CYCLOPHILIN BINDS CYCLOSPORIN A IN NEARLY IDENTICAL CONFORMATION AS HUMAN CYCLOPHILIN== | ||
<StructureSection load='1csa' size='340' side='right'caption='[[1csa]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1csa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Tolypocladium_inflatum Tolypocladium inflatum]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CSA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CSA FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | |||
- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=BMT:4-METHYL-4-[(E)-2-BUTENYL]-4,N-METHYL-THREONINE'>BMT</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=PRD_000142:Cyclosporin+A'>PRD_000142</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1csa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1csa OCA], [https://pdbe.org/1csa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1csa RCSB], [https://www.ebi.ac.uk/pdbsum/1csa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1csa ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The periplasmic Escherichia coli cyclophilin is distantly related to human cyclophilin (34% sequence identity). Peptidyl-prolyl isomerase activity, cyclosporin A binding, and inhibition of the calcium-dependent phosphatase calcineurin are compared for human and E. coli wild-type and mutant proteins. Like human cyclophilin, the E. coli protein is a cis-trans peptidyl-prolyl isomerase. However, while the human protein binds cyclosporin A tightly (Kd = 17 nM), the E. coli protein does not (Kd = 3.4 microM). The mutant F112W E. coli cyclophilin has enhanced cyclosporin binding (Kd = 170 nM). As for the human protein, the complex of the E. coli mutant with cyclosporin A inhibits calcineurin. Here we describe the structure at pH 6.2 of cyclosporin A bound to the mutant E. coli cyclophilin as solved with solution NMR methods. Despite the low overall sequence identity, the structure of the bound cyclosporin A is virtually identical in both proteins. To assess differences of the cyclosporin binding site, the solution structure of wild-type E. coli cyclophilin was compared with structures of uncomplexed human cyclophilin A and with cyclosporin bound. Despite the structural similarity of bound cyclosporin A, the architecture of the binding site in the E. coli protein is substantially different at the site most distant to tryptophan 121 (human sequence). This site is constructed by a five-residue insertion in a loop of the E. coli protein, replacing another loop in the human protein. | |||
The mutant Escherichia coli F112W cyclophilin binds cyclosporin A in nearly identical conformation as human cyclophilin.,Fejzo J, Etzkorn FA, Clubb RT, Shi Y, Walsh CT, Wagner G Biochemistry. 1994 May 17;33(19):5711-20. PMID:8180197<ref>PMID:8180197</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1csa" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cyclophilin 3D structures|Cyclophilin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
[[Category: Tolypocladium inflatum]] | |||
[[Category: Fejzo J]] | |||
== | [[Category: Wagner G]] | ||
[[Category: Walsh CT]] | |||
[[Category: | |||
[[Category: | |||
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Latest revision as of 08:26, 5 June 2024
THE MUTANT E.COLI F112W CYCLOPHILIN BINDS CYCLOSPORIN A IN NEARLY IDENTICAL CONFORMATION AS HUMAN CYCLOPHILINTHE MUTANT E.COLI F112W CYCLOPHILIN BINDS CYCLOSPORIN A IN NEARLY IDENTICAL CONFORMATION AS HUMAN CYCLOPHILIN
Structural highlights
Publication Abstract from PubMedThe periplasmic Escherichia coli cyclophilin is distantly related to human cyclophilin (34% sequence identity). Peptidyl-prolyl isomerase activity, cyclosporin A binding, and inhibition of the calcium-dependent phosphatase calcineurin are compared for human and E. coli wild-type and mutant proteins. Like human cyclophilin, the E. coli protein is a cis-trans peptidyl-prolyl isomerase. However, while the human protein binds cyclosporin A tightly (Kd = 17 nM), the E. coli protein does not (Kd = 3.4 microM). The mutant F112W E. coli cyclophilin has enhanced cyclosporin binding (Kd = 170 nM). As for the human protein, the complex of the E. coli mutant with cyclosporin A inhibits calcineurin. Here we describe the structure at pH 6.2 of cyclosporin A bound to the mutant E. coli cyclophilin as solved with solution NMR methods. Despite the low overall sequence identity, the structure of the bound cyclosporin A is virtually identical in both proteins. To assess differences of the cyclosporin binding site, the solution structure of wild-type E. coli cyclophilin was compared with structures of uncomplexed human cyclophilin A and with cyclosporin bound. Despite the structural similarity of bound cyclosporin A, the architecture of the binding site in the E. coli protein is substantially different at the site most distant to tryptophan 121 (human sequence). This site is constructed by a five-residue insertion in a loop of the E. coli protein, replacing another loop in the human protein. The mutant Escherichia coli F112W cyclophilin binds cyclosporin A in nearly identical conformation as human cyclophilin.,Fejzo J, Etzkorn FA, Clubb RT, Shi Y, Walsh CT, Wagner G Biochemistry. 1994 May 17;33(19):5711-20. PMID:8180197[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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