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Solution structure of the Legionella pneumophila Mip-rapamycin complex.

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Ceymann A, Horstmann M, Ehses P, Schweimer K, Paschke AK, Steinert M, Faber C
OpenAccess logo BMC Struct Biol 8 17 (2008)
Cited: 21 times
EuropePMC logo PMID: 18366641

Abstract

Background

Legionella pneumphila is the causative agent of Legionnaires' disease. A major virulence factor of the pathogen is the homodimeric surface protein Mip. It shows peptidyl-prolyl cis/trans isomerase activty and is a receptor of FK506 and rapamycin, which both inhibit its enzymatic function. Insight into the binding process may be used for the design of novel Mip inhibitors as potential drugs against Legionnaires' disease.

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.

Articles - 2vcd mentioned but not cited (2)

  1. Solution structure of the Legionella pneumophila Mip-rapamycin complex. Ceymann A, Horstmann M, Ehses P, Schweimer K, Paschke AK, Steinert M, Faber C. BMC Struct Biol 8 17 (2008)
  2. Inhibitor-induced conformational stabilization and structural alteration of a mip-like peptidyl prolyl cis-trans isomerase and its C-terminal domain. Polley S, Jana B, Chakrabarti G, Sau S. PLoS One 9 e102891 (2014)


Reviews citing this publication (7)

  1. Microbial peptidyl-prolyl cis/trans isomerases (PPIases): virulence factors and potential alternative drug targets. Ünal CM, Steinert M. Microbiol Mol Biol Rev 78 544-571 (2014)
  2. FKBP Ligands-Where We Are and Where to Go? Kolos JM, Voll AM, Bauder M, Hausch F. Front Pharmacol 9 1425 (2018)
  3. Peptidylprolyl cis-trans isomerases of Legionella pneumophila: virulence, moonlighting and novel therapeutic targets. Rasch J, Ünal CM, Steinert M. Biochem Soc Trans 42 1728-1733 (2014)
  4. Vaccine potential of bacterial macrophage infectivity potentiator (MIP)-like peptidyl prolyl cis/trans isomerase (PPIase) proteins. Humbert MV, Almonacid Mendoza HL, Jackson AC, Hung MC, Bielecka MK, Heckels JE, Christodoulides M. Expert Rev Vaccines 14 1633-1649 (2015)
  5. Protein sociology of ProA, Mip and other secreted virulence factors at the Legionella pneumophila surface. Scheithauer L, Karagöz MS, Mayer BE, Steinert M. Front Cell Infect Microbiol 13 1140688 (2023)
  6. Update on the Neisseria Macrophage Infectivity Potentiator-Like PPIase Protein. Christodoulides M. Front Cell Infect Microbiol 12 861489 (2022)
  7. Molecular chameleons in drug discovery. Poongavanam V, Wieske LHE, Peintner S, Erdélyi M, Kihlberg J. Nat Rev Chem 8 45-60 (2024)

Articles citing this publication (12)

  1. VBNC Legionella pneumophila cells are still able to produce virulence proteins. Alleron L, Khemiri A, Koubar M, Lacombe C, Coquet L, Cosette P, Jouenne T, Frere J. Water Res 47 6606-6617 (2013)
  2. A Burkholderia pseudomallei macrophage infectivity potentiator-like protein has rapamycin-inhibitable peptidylprolyl isomerase activity and pleiotropic effects on virulence. Norville IH, Harmer NJ, Harding SV, Fischer G, Keith KE, Brown KA, Sarkar-Tyson M, Titball RW. Infect Immun 79 4299-4307 (2011)
  3. Recent progress towards understanding genetic variation in the Mycobacterium abscessus complex. Howard ST. Tuberculosis (Edinb) 93 Suppl S15-20 (2013)
  4. A novel FK-506-binding-like protein that lacks peptidyl-prolyl isomerase activity is involved in intracellular infection and in vivo virulence of Burkholderia pseudomallei. Norville IH, Breitbach K, Eske-Pogodda K, Harmer NJ, Sarkar-Tyson M, Titball RW, Steinmetz I. Microbiology (Reading) 157 2629-2638 (2011)
  5. Collagen IV-derived peptide binds hydrophobic cavity of Legionella pneumophila Mip and interferes with bacterial epithelial transmigration. Ünal C, Schwedhelm KF, Thiele A, Weiwad M, Schweimer K, Frese F, Fischer G, Hacker J, Faber C, Steinert M. Cell Microbiol 13 1558-1572 (2011)
  6. Novel Cycloheximide Derivatives Targeting the Moonlighting Protein Mip Exhibit Specific Antimicrobial Activity Against Legionella pneumophila. Rasch J, Theuerkorn M, Ünal C, Heinsohn N, Tran S, Fischer G, Weiwad M, Steinert M. Front Bioeng Biotechnol 3 41 (2015)
  7. The structure of a Burkholderia pseudomallei immunophilin-inhibitor complex reveals new approaches to antimicrobial development. Norville IH, O'Shea K, Sarkar-Tyson M, Zheng S, Titball RW, Varani G, Harmer NJ. Biochem J 437 413-422 (2011)
  8. Broad-spectrum in vitro activity of macrophage infectivity potentiator inhibitors against Gram-negative bacteria and Leishmania major. Iwasaki J, Lorimer DD, Vivoli-Vega M, Kibble EA, Peacock CS, Abendroth J, Mayclin SJ, Dranow DM, Pierce PG, Fox D, Lewis M, Bzdyl NM, Kristensen SS, Inglis TJJ, Kahler CM, Bond CS, Hasenkopf A, Seufert F, Schmitz J, Marshall LE, Scott AE, Norville IH, Myler PJ, Holzgrabe U, Harmer NJ, Sarkar-Tyson M. J Antimicrob Chemother 77 1625-1634 (2022)
  9. Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation. Karagöz MS, Ünal CM, Mayer BE, Müsken M, Borrero-de Acuña JM, Steinert M. Infect Immun 90 e0027622 (2022)
  10. Proline substitutions in a Mip-like peptidyl-prolyl cis-trans isomerase severely affect its structure, stability, shape and activity. Polley S, Chakravarty D, Chakrabarti G, Chattopadhyaya R, Sau S. Biochim Open 1 28-39 (2015)
  11. Determining the roles of a conserved tyrosine residue in a Mip-like peptidyl-prolyl cis-trans isomerase. Polley S, Chakravarty D, Chakrabarti G, Sau S. Int J Biol Macromol 87 273-280 (2016)
  12. Backbone and side-chain ¹H, ¹³C and ¹⁵N assignments of the PPIase domain of macrophage infectivity potentiator (Mip) protein from Coxiella burnetii. Tse MK, Cheung SK, Ke YH, Lau CC, Sze KH, Yuen KY. Biomol NMR Assign 8 173-176 (2014)


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