| Protein-drug complexes important for immunoregulation and organ transplantation. | |
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MedLine Citation:
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PMID: 8994885 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recently, two structures of the Ser/Thr phosphorylase calcineurin in complex with FK506 and its cognate immunophilin, FKBP12, have been reported, both solved by small pharmaceutical companies focused on structure-based drug design. A realization, however, that the toxicities associated with calcineurin-mediated immunosuppressants might be mechanism based has driven the current interest in alternative approaches to autoimmunity prophylaxis and preventing transplant rejection. Regulatory approval in 1995 of the immunosuppressant prodrug mycophenolate mofetil, whose active metabolite, mycophenolic acid, inhibits inosine monophosphate dehydrogenase, has focused attention on the potential significance of the de novo purine-biosynthesis pathway as a target for immunosuppressive drugs, leading ultimately to the solution of enzyme structure as a drug design target. As this and other clinically relevant targets are discovered, elaborated and refined via the activity of their cognate agents (as was the case for the phosphatase calcineurin via the activity of cyclosporin), a critical opportunity should ensue for structural biology to exert a profound effect on the future development of these therapies. |
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Authors:
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M A Navia |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Current opinion in structural biology Volume: 6 ISSN: 0959-440X ISO Abbreviation: Curr. Opin. Struct. Biol. Publication Date: 1996 Dec |
Date Detail:
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Created Date: 1997-02-05 Completed Date: 1997-02-05 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9107784 Medline TA: Curr Opin Struct Biol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 838-47 Citation Subset: IM; X |
Affiliation:
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Vertex Pharmaceuticals Incorporated, Cambridge, MA 02139-4242, USA. navia@vpharm.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Calcineurin Calmodulin-Binding Proteins / antagonists & inhibitors Carrier Proteins / chemistry, pharmacology DNA-Binding Proteins / chemistry, pharmacology Drug Design Glucocorticoids / chemistry, pharmacology HIV / metabolism Heat-Shock Proteins / chemistry, pharmacology Immunosuppressive Agents / chemistry*, metabolism* Models, Molecular Molecular Structure Nucleotides / antagonists & inhibitors, biosynthesis Phosphoprotein Phosphatases / antagonists & inhibitors Protein Binding Protein Conformation Tacrolimus Binding Proteins Transplantation |
| Chemical | |
Reg. No./Substance:
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0/Calmodulin-Binding Proteins; 0/Carrier Proteins; 0/DNA-Binding Proteins; 0/Glucocorticoids; 0/Heat-Shock Proteins; 0/Immunosuppressive Agents; 0/Nucleotides; EC 3.1.3.16/Calcineurin; EC 3.1.3.16/Phosphoprotein Phosphatases; EC 5.2.1.-/Tacrolimus Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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