2Y78: Crystal Structure of Bpss1823, a Mip-like Chaperone From Burkholderia Pseudomallei

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: 2Y78Download
MMDB ID: 90714
PDB Deposition Date: 2011/1/28
Updated in MMDB: 2011/08 
Experimental Method:
x-ray diffraction
Resolution: 0.91  Å
Source Organism:
Similar Structures:
Biological Unit for 2Y78: dimeric; determined by author and by software (PISA)
Molecular Components in 2Y78
Label Count Molecule
Proteins (2 molecules)
2
Peptidyl-prolyl Cis-trans Isomerase
Molecule annotation
Chemicals (10 molecules)
1
4
2
4
3
2
* Click molecule labels to explore molecular sequence information.

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