ISSN:
0887-3585
Keywords:
protein minimization
;
protein engineering
;
disulfide mutant
;
Chemistry
;
Biochemistry and Biotechnology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Medicine
Notes:
The characteristic CXC chemokine disulfide core of interleukin-8 (IL-8) has been rearranged in a variant replacing the 9 - 50 disulfide with a 9 - 38 disulfide. The new variant has been characterized by its binding affinity to IL-8 receptors A and B and the erythrocyte receptor DARC. This variant binds the three receptors with affinities between 500- and 2,500-fold lower than wild-type IL-8. Binding affinity results are also reported for the variant with alanine substituted for both cysteines 9 and 50. The Glu38 → Cys/Cys50 → Ala IL-8 crystallizes in space group P212121 with cell parameters a = 46.4, b = 49.2, and c = 69.5 Å, and has been refined to an R-value of 19.4% for data from 10 to 2 Å resolution. Analysis of the structure confirms the new disulfide arrangement and suggests that changes at Ile10 may be the principal cause of the lowered affinities. © 1997 Wiley-Liss Inc.
Additional Material:
5 Ill.
Type of Medium:
Electronic Resource
