Electrochemical Characterization of Escherichia coli Adaptive Response Protein AidB

International Journal of Molecular Sciences

Michael J. Hamill²  Marco Jost¹  Cintyu Wong¹  Nicholas C. Bene²  Catherine L. Drennan¹ 

[1] Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, USA; E-Mails:;Department of Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA; E-Mails:

关键词: adaptive response;    DNA repair;    protein electrochemistry;    acyl-coenzyme A dehydrogenase;    flavin cofactor;    reduction potential;   

DOI  :  10.3390/ijms131216899

来源: mdpi

【 摘 要 】

When exposed to known DNA-damaging alkylating agents, Escherichia coli cells increase production of four DNA repair enzymes: Ada, AlkA, AlkB, and AidB. The role of three enzymes (Ada, AlkA, and AlkB) in repairing DNA lesions has been well characterized, while the function of AidB is poorly understood. AidB has a distinct cofactor that is potentially related to the elusive role of AidB in adaptive response: a redox active flavin adenine dinucleotide (FAD). In this study, we report the thermodynamic redox properties of the AidB flavin for the first time, both for free protein and in the presence of potential substrates. We find that the midpoint reduction potential of the AidB flavin is within a biologically relevant window for redox chemistry at −181 mV, that AidB significantly stabilizes the flavin semiquinone, and that small molecule binding perturbs the observed reduction potential. Our electrochemical results combined with structural analysis allow for fresh comparisons between AidB and the homologous acyl-coenzyme A dehydrogenase (ACAD) family of enzymes. AidB exhibits several discrepancies from ACADs that suggest a novel catalytic mechanism distinct from that of the ACAD family enzymes.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.