|1jvw, resolution 1.70Å ()|
TRYPANOSOMA CRUZI MACROPHAGE INFECTIVITY POTENTIATOR (TCMIP)
The macrophage infectivity potentiator protein from Trypanosoma cruzi (TcMIP) is a major virulence factor secreted by the etiological agent of Chagas' disease. It is functionally involved in host cell invasion. We have determined the three-dimensional crystal structure of TcMIP at 1.7 A resolution. The monomeric protein displays a peptidyl-prolyl cis-trans isomerase (PPIase) core, encompassing the characteristic rotamase hydrophobic active site, thus explaining the strong inhibition of TcMIP by the immunosuppressant FK506 and related drugs. In TcMIP, the twisted beta-sheet of the core is extended by an extra beta-strand, preceded by a long, exposed N-terminal alpha-helix, which might be a target recognition element. An invasion assay shows that the MIP protein from Legionella pneumophila (LpMIP), which has an equivalent N-terminal alpha-helix, can substitute for TcMIP. An additional exposed alpha-helix, this one unique to TcMIP, is located in the C-terminus of the protein. The high-resolution structure reported here opens the possibility for the design of new inhibitory drugs that might be useful for the clinical treatment of American trypanosomiasis.
Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed alpha-helix., Pereira PJ, Vega MC, Gonzalez-Rey E, Fernandez-Carazo R, Macedo-Ribeiro S, Gomis-Ruth FX, Gonzalez A, Coll M, EMBO Rep. 2002 Jan;3(1):88-94. Epub 2001 Dec 19. PMID:11751578
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[MIP_TRYCR] Essential virulence factor associated with macrophage infectivity. Exhibits PPIase activity.
About this Structure
- Pereira PJ, Vega MC, Gonzalez-Rey E, Fernandez-Carazo R, Macedo-Ribeiro S, Gomis-Ruth FX, Gonzalez A, Coll M. Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed alpha-helix. EMBO Rep. 2002 Jan;3(1):88-94. Epub 2001 Dec 19. PMID:11751578 doi:10.1093/embo-reports/kvf009