Download MendeleyNovel insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit F
Toh, Y.K., Balakrishna, A.M., Manimekalai, M.S.S., Chionh, B.B., Seetharaman, R.R.C., Eisenhaber, F., Eisenhaber, B., Gruber, G.(2017) Biochim Biophys Acta 1861: 3201-3214
- PubMed: 28935609
- DOI: https://doi.org/10.1016/j.bbagen.2017.09.011
- Primary Citation of Related Structures:
5H29 - PubMed Abstract:
The ability of the vancomycin-resistant Enterococcus faecalis (V583) to restore redox homeostasis via antioxidant defense mechanism is of importance, and knowledge into this defense is essential to understand its antibiotic-resistance and survival in hosts. The flavoprotein disulfide reductase AhpR, composed of the subunits AhpC and AhpF, represents one such vital part. Circular permutation was found to be a feature of the AhpF protein family. E. faecalis (V583) AhpF (EfAhpF) appears to be a representative of a minor subclass of this family, the typically N-terminal two-fold thioredoxin-like domain (NTD_N/C) is located at the C-terminus, whereas the pyridine nucleotide-disulfide oxidoreductase domain is encoded in the N-terminal part of its sequence. In EfAhpF, these two domains are connected via an unusually long linker region providing optimal communication between both domains. EfAhpF forms a dimer in solution similar to Escherichia coli AhpF. The crystallographic 2.3Å resolution structure of the NTD_N/C domain reveals a unique loop-helix stretch ( 409 ILKDTEPAKELLYGIEKM 426 ) not present in homologue domains of other prokaryotic AhpFs. Deletion of the unique 415 PAKELLY 421 -helix or of 415 PAKELL 420 affects protein stability or attenuates peroxidase activity. Furthermore, mutation of Y421 is described to be essential for E. faecalis AhpF's optimal NADH-oxidative activity.
Organizational Affiliation:
Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Republic of Singapore.
