Abstract | BACKGROUND: RESULTS: We have solved the solution structure of free Mip77-213 and the Mip77-213-rapamycin complex by NMR spectroscopy. Mip77-213 showed the typical FKBP-fold and only minor rearrangements upon binding of rapamycin. Apart from the configuration of a flexible hairpin loop, which is partly stabilized upon binding, the solution structure confirms the crystal structure. Comparisons to the structures of free FKBP12 and the FKBP12-rapamycin complex suggested an identical binding mode for both proteins. CONCLUSION: The structural similarity of the Mip- rapamycin and FKBP12-rapamycin complexes suggests that FKBP12 ligands may be promising starting points for the design of novel Mip inhibitors. The search for a novel drug against Legionnaires' disease may therefore benefit from the large variety of known FKBP12 inhibitors.
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Authors | Andreas Ceymann, Martin Horstmann, Philipp Ehses, Kristian Schweimer, Anne-Katrin Paschke, Michael Steinert, Cornelius Faber |
Journal | BMC structural biology
(BMC Struct Biol)
Vol. 8
Pg. 17
(Mar 17 2008)
ISSN: 1472-6807 [Electronic] England |
PMID | 18366641
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Bacterial Proteins
- Ligands
- Tacrolimus Binding Proteins
- Mip protein, Legionella pneumophila
- Peptidylprolyl Isomerase
- Sirolimus
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Topics |
- Amino Acid Sequence
- Anti-Bacterial Agents
(chemistry, metabolism)
- Bacterial Proteins
(chemistry, metabolism)
- Binding Sites
- Crystallography, X-Ray
- Humans
- Hydrogen Bonding
- Hydrophobic and Hydrophilic Interactions
- Legionella pneumophila
(enzymology, metabolism)
- Ligands
- Magnetic Resonance Spectroscopy
- Models, Molecular
- Molecular Sequence Data
- Peptidylprolyl Isomerase
(chemistry, metabolism)
- Protein Structure, Tertiary
- Sequence Alignment
- Sirolimus
(chemistry, metabolism)
- Tacrolimus Binding Proteins
(chemistry, metabolism)
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