| The regulatory domains of CNA have different effects on the inhibition of CN activity by FK506 and CsA. | |
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MedLine Citation:
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PMID: 17613169 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Calcineurin (CN) is the common receptor for two immunophilin-immunosuppressant complexes, Cyp-CsA and FKBP-FK506. Calcineurin is composed of a catalytic subunit (CNA) and a regulatory subunit (CNB). CNA contains the catalytic domain and three regulatory domains: a CNB-binding domain (BBH, 350-370), a calmodulin- binding domain (CBD, 389-413), and an autoinhibitory domain (AID, 457-482). To investigate the effects of these three regulatory domains on the inhibition of CN by the two drugs we constructed three C-terminal deletion mutants: CNAabc (1-456), CNAab (1-388) and CNAa (1-347). Inhibition of CNA and its derivatives by the two drugs was examined and compared with inhibition by peptides (AID [457-482] and LCBD [389-456], CBD and the extension of the AID were included). Our results show that the BBH is critical for inhibition of CN by Cyp-CsA and FKBP-FK506. The LCBD has no effect and the AID reduces the inhibition of CN by two complexes. In addition, LCBD and AID as autoinhibitors may inhibit enzyme activity via different sites. |
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Authors:
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Hai-Long Wang; Yan-Wei Du; Ben-Qiong Xiang; Wei-Lin Lin; Qun Wei |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: IUBMB life Volume: 59 ISSN: 1521-6543 ISO Abbreviation: IUBMB Life Publication Date: 2007 Jun |
Date Detail:
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Created Date: 2007-07-06 Completed Date: 2008-01-07 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 100888706 Medline TA: IUBMB Life Country: England |
Other Details:
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Languages: eng Pagination: 388-93 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing, PR China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcineurin / antagonists & inhibitors*, genetics, metabolism* Cyclophilin A / genetics, metabolism Cyclosporine / metabolism* Immunosuppressive Agents / metabolism* Mutation Peptides / genetics, metabolism Protein Structure, Tertiary Protein Subunits / antagonists & inhibitors*, genetics, metabolism* Rats Tacrolimus / metabolism* Tacrolimus Binding Protein 1A / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Immunosuppressive Agents; 0/Peptides; 0/Protein Subunits; 109581-93-3/Tacrolimus; 59865-13-3/Cyclosporine; EC 3.1.3.16/Calcineurin; EC 5.2.1.-/Cyclophilin A; EC 5.2.1.-/Tacrolimus Binding Protein 1A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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