Format

Send to

Choose Destination
Sci Rep. 2017 Aug 8;7(1):7609. doi: 10.1038/s41598-017-07716-5.

The FAD synthetase from the human pathogen Streptococcus pneumoniae: a bifunctional enzyme exhibiting activity-dependent redox requirements.

Author information

1
Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, Spain.
2
Instituto de Biocomputación y Física de Sistemas Complejos (BIFI) and GBsC-CSIC and BIFI-CSIC Joint Units, Universidad de Zaragoza, Zaragoza, Spain.
3
Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, School of Dentistry, University of Copenhagen, Copenhagen, DK-2200, Denmark.
4
Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, E-28040, Madrid, Spain.
5
Laboratorio de Microscopías Avanzadas (LMA), Instituto de Nanociencia de Aragón (INA), and Fundación INA, Universidad de Zaragoza, Zaragoza, Spain.
6
Univ Reims, Lab Rech Nanosci, EA4682, F-51100 Reims and INRA, FARE Lab, F-51100, Reims, France.
7
Fundación ARAID, Diputación General de Aragón, Aragón, Spain.
8
Aragon Institute for Health Research (IIS Aragon), Zaragoza, 50009, Spain.
9
Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, Spain. mmedina@unizar.es.
10
Instituto de Biocomputación y Física de Sistemas Complejos (BIFI) and GBsC-CSIC and BIFI-CSIC Joint Units, Universidad de Zaragoza, Zaragoza, Spain. mmedina@unizar.es.
11
Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, Spain. mmartine@unizar.es.
12
Instituto de Biocomputación y Física de Sistemas Complejos (BIFI) and GBsC-CSIC and BIFI-CSIC Joint Units, Universidad de Zaragoza, Zaragoza, Spain. mmartine@unizar.es.

Abstract

Prokaryotic bifunctional FAD synthetases (FADSs) catalyze the biosynthesis of FMN and FAD, whereas in eukaryotes two enzymes are required for the same purpose. FMN and FAD are key cofactors to maintain the flavoproteome homeostasis in all type of organisms. Here we shed light to the properties of the hitherto unstudied bacterial FADS from the human pathogen Streptococcus pneumoniae (SpnFADS). As other members of the family, SpnFADS catalyzes the three typical activities of prokaryotic FADSs: riboflavin kinase (RFK), ATP:FMN:adenylyltransferase (FMNAT), and FAD pyrophosphorylase (FADpp). However, several SpnFADS biophysical properties differ from those of other family members. In particular; i) the RFK activity is not inhibited by the riboflavin (RF) substrate, ii) the FMNAT and FADSpp activities require flavin substrates in the reduced state, iii) binding of adenine nucleotide ligands is required for the binding of flavinic substrates/products and iv) the monomer is the preferred state. Collectively, our results add interesting mechanistic differences among the few prokaryotic bifunctional FADSs already characterized, which might reflect the adaptation of the enzyme to relatively different environments. In a health point of view, differences among FADS family members provide us with a framework to design selective compounds targeting these enzymes for the treatment of diverse infectious diseases.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center