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Streptococcus pyogenes quinolinate‐salvage pathway—structural and functional studies of quinolinate phosphoribosyl transferase and NH 3 ‐dependent NAD + synthetase
Author(s) -
Booth William T.,
Morris Trevor L.,
Mysona David P.,
Shah Milan J.,
Taylor Linda K.,
Karlin Taylor W.,
Clary Kathryn,
Majorek Karolina A.,
Offermann Lesa R.,
Chruszcz Maksymilian
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14136
Subject(s) - nad+ kinase , quinolinate , streptococcus pyogenes , biology , nicotinamide adenine dinucleotide , microbiology and biotechnology , biochemistry , transferase , enzyme , cofactor , bacteria , genetics , amino acid , staphylococcus aureus , tryptophan , quinolinic acid
Streptococcus pyogenes , also known as Group A Strep ( GAS ), is an obligate human pathogen that is responsible for millions of infections and numerous deaths per year. Infection manifestations can range from simple, acute pharyngitis to more complex, necrotizing fasciitis. To date, most treatments for GAS infections involve the use of common antibiotics including tetracycline and clindamycin. Unfortunately, new strains have been identified that are resistant to these drugs, therefore, new targets must be identified to treat drug‐resistant strains. This work is focused on the structural and functional characterization of three proteins: spNadC, spNadD, and spNadE. These enzymes are involved in the biosynthesis of nicotinamide adenine dinucleotide ( NAD + ). The structures of spNadC and spNadE were determined. SpNadC is suggested to play a role in GAS virulence, while spNadE, functions as an NAD synthetase and is considered to be a new drug target. Determination of the spNadE structure uncovered a putative, NH 3 channel, which may provide insight into the mechanistic details of NH 3 ‐dependent NAD + synthetases in prokaryotes. Enzymes Quinolinate phosphoribosyltransferase: EC2.4.2.19 and NAD synthetase: EC6.3.1.5 . Database Protein structures for spNadC, spNadC Δ69A , and spNadE are deposited into Protein Data Bank under the accession codes 5HUL , 5HUO & 5HUP , and 5HUH & 5HUJ , respectively.