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Crystallization and preliminary X-ray diffraction analysis of the complex between a human anti-interferon antibody fragment and human interferon alpha-2A.


ABSTRACT: Recombinant human interferon alpha-2A (rhIFN-alpha-2A) has been crystallized in complex with the recombinantly produced Fab fragment of a therapeutic monoclonal antibody (MEDI545; IgG1/kappa) which targets several human interferon alpha subtypes. This constitutes the first reported crystals of a human type I interferon bound to an antibody. The orthorhombic crystals belonged to either space group I222 or I2(1)2(1)2(1), with unit-cell parameters a = 134.82, b = 153.26, c = 163.49 A. The diffraction of the crystals extended to 3.0 A resolution. The asymmetric unit contained two Fab-rhIFN-alpha-2A complexes. This corresponded to a crystal volume per protein weight (V(M)) of 3.02 A(3) Da(-1) and a solvent content of 59.3%. The corresponding three-dimensional structure is expected to shed light on the mechanism of action of MEDI545 and the molecular basis of its specificity.

SUBMITTER: Oganesyan V 

PROVIDER: S-EPMC2628856 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Crystallization and preliminary X-ray diffraction analysis of the complex between a human anti-interferon antibody fragment and human interferon alpha-2A.

Oganesyan Vaheh V   Damschroder Melissa M MM   Cook Kimberly E KE   Wu Herren H   Dall'Acqua William F WF  

Acta crystallographica. Section F, Structural biology and crystallization communications 20081225 Pt 1


Recombinant human interferon alpha-2A (rhIFN-alpha-2A) has been crystallized in complex with the recombinantly produced Fab fragment of a therapeutic monoclonal antibody (MEDI545; IgG1/kappa) which targets several human interferon alpha subtypes. This constitutes the first reported crystals of a human type I interferon bound to an antibody. The orthorhombic crystals belonged to either space group I222 or I2(1)2(1)2(1), with unit-cell parameters a = 134.82, b = 153.26, c = 163.49 A. The diffracti  ...[more]

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