RT Journal Article
T1 Crystal structure of glyceraldehyde-3-phosphate dehydrogenase from the Gram-positive bacterial pathogen A. vaginae, an immunoevasive factor that interacts with the human C5a anaphylatoxin
A1 Querol García, Javier
A1 Fernández, Francisco J.
A1 Marín Marín, Ana Victoria
A1 Gómez, Sara
A1 Fullà, Daniel
A1 Melchor Tafur, Cecilia
A1 Franco Hidalgo, Virginia
A1 Albertí, Sebastián
A1 Juanhuix, Jordi
A1 Rodríguez de Córdoba, Santiago
A1 Regueiro González-Barros, José Ramón
A1 Vega, María Cristina
AB The Gram-positive anaerobic human pathogenic bacterium Atopobium vaginae causes most diagnosed cases of bacterial vaginosis as well as opportunistic infections in immunocompromised patients. In addition to its well-established role in carbohydrate metabolism, D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Streptococcus pyogenes and S. pneumoniae have been reported to act as extracellular virulence factors during streptococcal infections. Here, we report the crystal structure of GAPDH from A. vaginae (AvGAPDH) at 2.19 Å resolution. The refined model has a crystallographic Rfree of 22.6%. AvGAPDH is a homotetramer wherein each subunit is bound to a nicotinamide adenine dinucleotide (NAD+) molecule. The AvGAPDH enzyme fulfills essential glycolytic as well as moonlight (non-glycolytic) functions, both of which might be targets of chemotherapeutic intervention. We report that AvGAPDH interacts in vitro with the human C5a anaphylatoxin and inhibits C5a-specific granulocyte chemotaxis, thereby suggesting the participation of AvGAPDH in complement-targeted immunoevasion in a context of infection. The availability of high-quality structures of AvGAPDH and other homologous virulence factors from Gram-positive pathogens is critical for drug discovery programs. In this study, sequence and structural differences between AvGAPDH and related bacterial and eukaryotic GAPDH enzymes are reported in an effort to understand how to subvert the immunoevasive properties of GAPDH and evaluate the potential of AvGAPDH as a druggable target.
PB Frontiers Media
YR 2017
FD 2017-04-10
LK https://hdl.handle.net/20.500.14352/107450
UL https://hdl.handle.net/20.500.14352/107450
LA eng
NO Querol-García J, Fernández FJ, Marin AV, Gómez S, Fullà D, Melchor-Tafur C, Franco-Hidalgo V, Albertí S, Juanhuix J, Rodríguez de Córdoba S, Regueiro JR, Vega MC. Crystal Structure of Glyceraldehyde-3-Phosphate Dehydrogenase from the Gram-Positive Bacterial Pathogen A. vaginae, an Immunoevasive Factor that Interacts with the Human C5a Anaphylatoxin. Front Microbiol. 2017 Apr 10;8:541. doi: 10.3389/fmicb.2017.00541. PMID: 28443070; PMCID: PMC5385343.
NO Instituto de Salud Carlos III
NO Ministerio de Economía y Competitividad (España)
NO Comunidad de Madrid
NO European Commission
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 6 abr 2025