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oai:repisalud.isciii.es:20.500.12105/204232024-11-28T15:57:04Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16938col_20.500.12105_16967
Repisalud author Querol-Garcia, Javier author Fernandez, Francisco J author Marin, Ana V author Gomez, Sara author Fulla, Daniel author Melchor-Tafur, Cecilia author Franco-Hidalgo, Virginia author Albert, Sebastian author Juanhuix, Jordi author Rodriguez de Cordoba, Santiago author Regueiro, Jose R author Cristina Vega, M 2024-07-11T09:07:45Z 2024-07-11T09:07:45Z 2017-04-10 Querol-Garcia J, Fernandez FJ, Marin AV, Gomez S, Fulla D, Melchor-Tafur C, et al. 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. 10.3389/fmicb.2017.00541 1664-302X Frontiers in Microbiology http://hdl.handle.net/20.500.13003/9868 28443070 L615712534 2-s2.0-85018291369 http://hdl.handle.net/20.500.12105/20423 398656400001 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 (A) over circle resolution. The refined model has a crystallographic R-free 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. eng Anaphylatoxin Chemoattraction Complement system C5a GAPDH (glyceraldehyde-3-phosphate dehydrogenase) gram-positive pathogen Immunoevasion x-ray crystallography 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 research article