4hy7

Publication Abstract from PubMed

Cyclophilins belong to a family of proteins that bind to the immunosuppressive drug cyclosporin A (CsA). Several members of this protein family catalyze the cis-trans isomerization of peptide bonds preceding prolyl residues. The present study describes the biochemical and structural characteristics of a cytosolic cyclophilin (TaCypA-1) cloned from wheat (Triticum aestivum L.). Purified TaCypA-1 expressed in Escherichia coli showed peptidyl-prolyl cis-trans isomerase activity, which was inhibited by CsA with an inhibition constant of 78.3 nM. The specific activity and catalytic efficiency (kcat/Km) of the purified TaCypA-1 were 99.06 +/- 0.13 nmol s(-1) mg(-1) and 2.32 x 10(5) M(-1) s(-1), respectively. The structures of apo TaCypA-1 and the TaCypA-1-CsA complex were determined at 1.25 and 1.20 A resolution, respectively, using X-ray diffraction. Binding of CsA to the active site of TaCypA-1 did not result in any significant conformational change in the apo TaCypA-1 structure. This is consistent with the crystal structure of the human cyclophilin D-CsA complex reported at 0.96 A resolution. The TaCypA-1 structure revealed the presence of a divergent loop of seven amino acids (48)KSGKPLH(54) which is a characteristic feature of plant cyclophilins. This study is the first to elucidate the structure of an enzymatically active plant cyclophilin which shows peptidyl-prolyl cis-trans isomerase activity and the presence of a divergent loop.

Structural and biochemical characterization of the cytosolic wheat cyclophilin TaCypA-1.,Sekhon SS, Kaur H, Dutta T, Singh K, Kumari S, Kang S, Park SG, Park BC, Jeong DG, Pareek A, Woo EJ, Singh P, Yoon TS Acta Crystallogr D Biol Crystallogr. 2013 Apr;69(Pt 4):555-63. doi:, 10.1107/S0907444912051529. Epub 2013 Mar 9. PMID:23519664^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.