2KE0
Solution structure of peptidyl-prolyl cis-trans isomerase from Burkholderia pseudomallei
Summary for 2KE0
| Entry DOI | 10.2210/pdb2ke0/pdb |
| Related | 1FKL |
| Descriptor | Peptidyl-prolyl cis-trans isomerase (1 entity in total) |
| Functional Keywords | peptidyl-prolyl cis-trans isomerase, bupsa.00130.a, fk506 binding protein fkbp, isomerase, structural genomics, seattle structural genomics center for infectious disease, ssgcid |
| Biological source | Burkholderia pseudomallei (Pseudomonas pseudomallei) |
| Total number of polymer chains | 1 |
| Total formula weight | 12239.70 |
| Authors | Zheng, S.,Leeper, T.,Napuli, A.,Nakazawa, S.H.,Varani, G.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2009-01-21, release date: 2009-03-03, Last modification date: 2024-05-01) |
| Primary citation | Norville, I.H.,O'Shea, K.,Sarkar-Tyson, M.,Zheng, S.,Titball, R.W.,Varani, G.,Harmer, N.J. The structure of a Burkholderia pseudomallei immunophilin-inhibitor complex reveals new approaches to antimicrobial development. Biochem.J., 437:413-422, 2011 Cited by PubMed 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 TGFβRI (transforming growth factor β 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. PubMed: 21574961DOI: 10.1042/BJ20110345 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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