Publication Date:
1991-05-10
Description:
Immunophilins, when complexed to immunosuppressive ligands, appear to inhibit signal transduction pathways that result in exocytosis and transcription. The solution structure of one of these, the human FK506 and rapamycin binding protein (FKBP), has been determined by nuclear magnetic resonance (NMR). FKBP has a previously unobserved antiparallel beta-sheet folding topology that results in a novel loop crossing and produces a large cavity lined by a conserved array of aromatic residues; this cavity serves as the rotamase active site and drug-binding pocket. There are other significant structural features (such as a protruding positively charged loop and an apparently flexible loop) that may be involved in the biological activity of FKBP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Michnick, S W -- Rosen, M K -- Wandless, T J -- Karplus, M -- Schreiber, S L -- GM-30804/GM/NIGMS NIH HHS/ -- GM-38627/GM/NIGMS NIH HHS/ -- I-S10-RR04870/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1991 May 10;252(5007):836-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1709301" target="_blank"〉PubMed〈/a〉
Keywords:
Anti-Bacterial Agents/metabolism
;
Binding Sites
;
Carrier Proteins/*ultrastructure
;
Crystallography
;
Humans
;
Immunosuppressive Agents/metabolism
;
Magnetic Resonance Spectroscopy
;
Molecular Structure
;
Polyenes/metabolism
;
Sirolimus
;
Tacrolimus
;
Tacrolimus Binding Proteins
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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