2Y78

Crystal structure of BPSS1823, a Mip-like chaperone from Burkholderia pseudomallei

2Y78 の概要

• エントリーDOI: 10.2210/pdb2y78/pdb
• 分子名称: PEPTIDYL-PROLYL CIS-TRANS ISOMERASE, SULFATE ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: isomerase, mip, ppiase, virulence
• 由来する生物種: BURKHOLDERIA PSEUDOMALLEI
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14524.54

構造登録者

Norville, I.H.,O'Shea, K.,Sarkar-Tyson, M.,Harmer, N.J. (登録日: 2011-01-28, 公開日: 2011-05-25, 最終更新日: 2023-12-20)

主引用文献

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-, 2011

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: 21574961
DOI: 10.1042/BJ20110345

実験手法

X-RAY DIFFRACTION (0.91 Å)