PDBsum entry 1jvw

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Isomerase PDB id
Protein chain
160 a.a. *
Waters ×271
* Residue conservation analysis

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Key reference
Title Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed alpha-Helix.
Authors P.J.Pereira, M.C.Vega, E.González-Rey, R.Fernández-Carazo, S.Macedo-Ribeiro, F.X.Gomis-Rüth, A.González, M.Coll.
Ref. EMBO Rep, 2002, 3, 88-94. [DOI no: 10.1093/embo-reports/kvf009]
PubMed id 11751578
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.
Figure 1.
Figure 1 Structure of TcMIP. (A) Amino acid sequence alignment of TcMIP (SWISSPROT entry MIP_TRYCR) with bacterial MIPs from L. pneumophila (SWISSPROT entry MIP_LEGPN), Vibrio cholerae (SWISSPROT entry Q9KP11) and C. trachomatis (SWISSPROT entry MIP_CHLTR), with human FKBP12 (SWISSPROT entry FKB1_HUMAN) and FKBP-like protein from E. coli (SWISSPROT entry FKBB_ECOLI). Residues conserved in all sequences are highlighted in green, those identical to TcMIP in yellow. Signal peptide regions have been omitted. Residues forming the hydrophobic active-site pocket are indicated by blue triangles. The numbering and the secondary structure elements of TcMIP are displayed above the alignment. -Helices are shown in red, -strands in green. (B) Overall structure of TcMIP, with the secondary structure elements shown in red ( -helices) and green ( -strands). The side chains of important residues in the active site of the enzyme are depicted as ball-and-stick models, with carbon atoms in yellow, oxygens in red and nitrogens in blue.
Figure 2.
Figure 2 TcMIP is homologous to other FK506-binding proteins. (A) Stereo view of the C[ ]trace of TcMIP (red) superimposed with those of L. pneumophila MIP (blue; PDB code 1FD9) and human FKBP12 (yellow; PDB code 1FKJ). (B) Stereo close-up view of the active site of TcMIP (atom colour code) superimposed with that of the human FKBP12 -FK506 complex (green; PDB code 1bkf) and the FKBP12 -rapamycin complex (blue; PDB code 1c9h). Some key residues and regions of the immunosuppressors discussed in the text are labeled.
The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO Rep (2002, 3, 88-94) copyright 2002.
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