Disease relevance of PPID

• Biochemical and calmodulin binding properties of estrogen receptor binding cyclophilin expressed in Escherichia coli [1].

High impact information on PPID

• Deletion mutants of CyP-40 fused to glutathione S-transferase were immobilized on glutathione-agarose and then used in a rapid hsp90 retention assay to define regions of the CyP-40 C terminus that are important for hsp90 binding [2].
• By preincubating myometrial cytosol with lysates containing bacterially expressed FKBP52, we have shown that FKBP52 competes with CyP-40 for hsp90 binding [2].
• We propose that the tetratricopeptide repeat domain mediates the protein interaction properties of ERBC and p59 [3].
• Homology analyses confirm that ERBC is a new member of the cyclophilin family and contains a C-terminal domain with significant sequence homology to an internal region of p59, a binding protein for the immunosuppressant FK506 (FKBP59) [3].
• We have chemically determined the amino acid sequences of eight peptides derived from the 40-kDa component and now report the cloning and primary sequence of a cDNA encoding this protein, which is designated estrogen receptor-binding cyclophilin (ERBC) [3].

Biological context of PPID

• The C-terminal residues of Cyp40 protrude out beyond the body of the TPR domain to form a charged helix-the putative calmodulin binding site [4].
• With N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as substrate, GST-ERBC demonstrated a kcat/KM value of 5.1 x 10(5) M-1s-1 at 5 degrees C. The isomerase activity was inhibited by cyclosporin A with an IC50 value of 1030 nM [1].

Associations of PPID with chemical compounds

• These values indicate that ERBC has a decreased catalytic efficiency and sensitivity to cyclosporin A relative to human cyclophilin [1].

Analytical, diagnostic and therapeutic context of PPID

• Purification, characterization and crystallization in two crystal forms of bovine cyclophilin 40 [5].

References