Crystal structure of cyclophilin A in complex with Voclosporin E-ISA247

2,4,5-trideoxy-2-(methylamino)-4-[(2E)-penta-2,4-dien-1-yl]-L-xylonic acid

Structural basis for the cyclophilin A binding affinity and immunosuppressive potency of E-ISA247 (voclosporin).

20% PEG3350, 0.1M MES, 0.2M ammonium sulphate, pH 6.5, VAPOR DIFFUSION, HANGING DROP, temperature 295K

CRYSTAL STRUCTURE OF CYCLOPHILIN A IN COMPLEX WITH THE TRANS ISOMER VOCLOSPORIN Z-ISA247

VOCLOSPORIN IS A CYCLOSPORIN ANALOG, A CYCLIC UNDECAPEPTIDE. HERE, VOCLOSPORIN IS REPRESENTED BY THE SEQUENCE (SEQRES). RESIDUE 1 IS LINKED TO RESIDUE 11 VIA A PEPTIDE BOND. IT DIFFERS FROM CYCLOSPORIN A IN POSITION 5. AUTHOR STATES THAT THE E-ISA247 (VOCLOSPORIN) ANTIBIOTIC IN THIS STRUCTURE IS NOT NATURAL PRODUCT, RATHER IT IS NEWLY DESIGNED COMPOUND. THE CLOSEST MATCH IN NORINE DATABASE IS CYCLOSPORIN A, WITH A DIFFERENCE AT RESIDUE 5 ALTERED FROM N-METHYL-4-BUTENYL-4-METHYL THREONINE (WITH PROTEIN DATA BANK LIGAND CODE BMT) TO 2,4,5-TRIDEOXY-2-(METHYLAMINO)-4-[(2E)-PENTA-2,4-DIEN-1-YL]-L-XYLONIC ACID(LIGAND CODE XXA)

The asymmetric unit of the crystal contains ten pharmacological units.

CALCINEURIN INHIBITION, CALCINEURIN, CYCLOSPORIN, PSORIASIS, IMMUNOSUPPRESSANT, VOCLOSPORIN, ISOMERASE-IMMUNOSUPPRESSANT COMPLEX