Crystal structures of Leptospira interrogans FAD-containing ferredoxin-NADP+

NASCIMENTO, A. S; CATALANO-DUPUY, D. L.; BERNARDES, A.; DE OLIVEIRA NETO, M; SANTOS, M.A.; CECCARELLI, E. A.; POLIKARPOV, I.

BMC Structural Biology

BioMed Central Ltd.

Lugar: London, UK; Año: 2007 vol. 7 p. 1 - 12

1472-6807

Background:  Ferredoxin-NADP(H)  reductases  (FNRs)  are  flavoenzymes  that  catalyze the  electron  transfer  between  NADP(H)  and  the  proteins  ferredoxin  or  flavodoxin.  A number  of  structural  features  distinguish  plant and bacterial FNRs, one  of which  is  the mode  of  the  cofactor  FAD  binding.  Leptospira  interrogans  is  a  spirochaete  parasitic bacterium capable of infecting humans and mammals in general. Leptospira interrogans FNR  (LepFNR)  displays  low  sequence  identity  with  plant  (34%  with  Zea  mays)  and bacterial  (31% with Escherichia coli) FNRs. However, LepFNR contains all consensus sequences that define the plastidic class FNRs. Results: The crystal  structures of  the FAD-containing LepFNR and the complex of  the enzyme  with  NADP+,  were  solved  and  compared  to  known  FNRs.  The  comparison reveals significant structural similarities of the enzyme with the plastidic type FNRs and differences  with  the  bacterial  enzymes.  Our  small  angle  X-ray  scattering  experiments show that LepFNR is a monomeric enzyme. Moreover, our biochemical data demonstrate that  the  LepFNR  has  an  enzymatic  activity  similar  to  those  reported  for  the  plastidic enzymes  and  that  is  significantly  different  from  bacterial  flavoenzymes, which  display lower turnover rates. Conclusion: LepFNR is the first plastidic type FNR found in bacteria and, despite of its low  sequence  similarity with  plastidic FNRs  still  displays  high  catalytic  turnover  rates. The  typical  structural  and  biochemical  characteristics  of  plant  FNRs  unveiled  for LepFNR  support  a  notion  of  a  putative  lateral  gene  transfer which  presumably  offers Leptospira  interrogans  evolutionary  advantages.  The  wealth  of  structural  information about  LepFNR  provides  a  molecular  basis  for  advanced  drugs  developments  against leptospirosis.