Crystal structure and mutants of interleukin-1.beta....

Details Crystal structure and mutants of interleukin-1.beta.... Crystal structure and mutants of interleukin-1.beta....

C - Chemistry, Metallurgy

12

N

C12N 9/64 (2006.01) C12Q 1/37 (2006.01)

Patent

CA 2192485

Interleukin-1.beta. converting enzyme ("ICE") processes an inactive precursor to the pro-inflammatory cytokine, interleukin-1.beta.. The high-resolution structure of human ICE crystallized in complex with an inhibitor is determined by X-ray diffraction. The active site spans both the 10 and 20 kilodalton subunits. The accessory binding site is composed of residues from the p10 and p20 subunits that are adjacent to the two-fold axis of the crystal. The structure coordinates of the enzyme may be used to design novel classes of ICE inhibitors.

L'enzyme de conversion de l'interleukine-1.beta. (ICE) traite un précurseur inactif de la cytokine pro-inflammatoire, l'interleukine-1.beta.. La structure à résolution élevée de l'ICE de l'homme, cristallisée en complexe avec un inhibiteur, est déterminée au moyen d'un procédé de diffraction des rayons X. Le site actif s'étend à la fois aux sous-ensembles de 10 et 20 kilodaltons. Le site de fixation accessoire est composé de résidus provenant des sous-ensembles p10 et p20 contigus à l'axe brisé du cristal. Les coordonnées de la structure de l'enzyme peuvent s'utiliser pour créer de nouvelles catégories d'inhibiteurs de l'ICE.

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