1DYW

Biochemical and structural characterization of a divergent loop cyclophilin from Caenorhabditis elegans

1DYW の概要

• エントリーDOI: 10.2210/pdb1dyw/pdb
• 分子名称: CYCLOPHILIN 3 (2 entities in total)
• 機能のキーワード: isomerase(peptidyl-prolyl cis-trans), isomerase, rotamase
• 由来する生物種: CAENORHABDITIS ELEGANS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18576.18

構造登録者

Dornan, J.,Page, A.P.,Taylor, P.,Wu, S.Y.,Winter, A.D.,Husi, H.,Walkinshaw, M.D. (登録日: 2000-02-10, 公開日: 2000-06-22, 最終更新日: 2023-12-06)

主引用文献

Dornan, J.,Page, A.P.,Taylor, P.,Wu, S.Y.,Winter, A.D.,Husi, H.,Walkinshaw, M.D.
Biochemical and Structural Characterization of a Divergent Loop Cyclophilin from Caenorhabditis Elegans
J.Biol.Chem., 274:34877-, 1999

PubMed Abstract: Cyclophilin 3 (CYP-3) is one of the most abundantly expressed cyclophilin isoforms in the free living nematode Caenorhabditis elegans. The detailed post-embryonic expression pattern of the cyp-3 transcript is unusual, peaking during early larval development. The spatial expression pattern was examined via reporter gene analysis demonstrating that the cyp-3 transcript is exclusively expressed in the single anterior excretory cell. Recombinant cyclophilin 3 has been purified, crystallized and solved to a resolution of 1.8 A. The peptidyl-prolyl isomerase activity of CYP-3 has been characterized against the substrate N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, and gives a k(cat)/K(m) value of 2.4 x 10(6) M(-1) s(-1). The immunosuppressive drug cyclosporin A binds and inhibits CYP-3 with an IC(50) value of 16 nM, comparable with the range of values found for human cyclophilin A. The x-ray structure shows that the overall fold and active site geometry is similar to other cyclophilin structures. There are however a number of distinctive features, and we use this structure and amino acid sequence alignment analysis to identify a subgroup of "divergent-loop cyclophilins". This subgroup has a number of uniquely conserved features: an additional loop between residues 48 and 54 (KSGKPLH); two cysteine residues (Cys(40) and Cys(168)) that are in close proximity but remain in the unoxidized form, and two other conserved residues, His(54) and Glu(83). We suggest that these features are functionally important for the role played by this class of cyclophilins during cellular responses to stress caused by changes in the redox environment or by up-regulation of cellular activity. This study represents a detailed biological, biochemical, and structural characterization of a single cyclophilin isoform in the model organism Caenorhabditis elegans.

PubMed: 10574961
DOI: 10.1074/JBC.274.49.34877

実験手法

X-RAY DIFFRACTION (1.8 Å)