2KO7: Solution structure of peptidyl-prolyl cis-trans isomerase from Burkholderia pseudomallei complexed with Cycloheximide-N-ethylethanoate

Citation:
Abstract
Mips (macrophage infectivity potentiators) are a subset of immunophilins associated with virulence in a range of micro-organisms. These proteins possess peptidylprolyl isomerase activity and are inhibited by drugs including rapamycin and tacrolimus. We determined the structure of the Mip homologue [BpML1 (Burkholderia pseudomallei Mip-like protein 1)] from the human pathogen and biowarfare threat B. pseudomallei by NMR and X-ray crystallography. The crystal structure suggests that key catalytic residues in the BpML1 active site have unexpected conformational flexibility consistent with a role in catalysis. The structure further revealed BpML1 binding to a helical peptide, in a manner resembling the physiological interaction of human TGFbetaRI (transforming growth factor beta receptor I) with the human immunophilin FKBP12 (FK506-binding protein 12). Furthermore, the structure of BpML1 bound to the class inhibitor cycloheximide N-ethylethanoate showed that this inhibitor mimics such a helical peptide, in contrast with the extended prolyl-peptide mimicking shown by inhibitors such as tacrolimus. We suggest that Mips, and potentially other bacterial immunophilins, participate in protein-protein interactions in addition to their peptidylprolyl isomerase activity, and that some roles of Mip proteins in virulence are independent of their peptidylprolyl isomerase activity.
PDB ID: 2KO7Download
MMDB ID: 76966
PDB Deposition Date: 2009/9/11
Updated in MMDB: 2011/11
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 2KO7: monomeric; determined by author
Molecular Components in 2KO7
Label Count Molecule
Protein (1 molecule)
1
Peptidyl-prolyl Cis-trans Isomerase
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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