x-ray structures of two forms of the antibiotic oligomycin A: an inhibitor of ATP synthase

作者：Palmer Rex A^*; Ladd Mark; Howlin Brendan; Lisgarten David R

来源：Future Medicinal Chemistry, 2013, 5(8): 881-893.

DOI：10.4155/FMC.13.68

Background: Corrections to the chemical and x-ray structures of two forms of the antibiotic oligomycin A are presented: the original and best known, form (E), from Streptomyces diastatochromogenes, and a new form (C) from Streptomyces diastaticus. Method: The crystal structures are isomorphous, crystallizing in space group P2(1)2(1)2(1), with Z = 4[C45H73O11.CH3OH] per unit cell. Oligomycin A(E) refined with RI = 0.0734, using Cu K alpha x-radiation; and for Oligomycin A(C) RI = 0.0651 using Mo K alpha x-radiation. Conclusion: Serious corrections to the previously published structure of oligomycin A(C) are discussed and implemented. As a supplementary study geometry optimization of side group R4 of oligomycin A(E) was undertaken and achieved by energy minimization. These additional results clearly confirm the delocalization in this region observed in both x-ray structures. This result is contrary to the generally accepted formulation. Knowledge of the correct structures is important to those involved in the study and applications of the pharmacological and biological properties of these materials.

• 出版日期2013-5