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dc.contributor.author | Querol-Garcia, Javier | |
dc.contributor.author | Fernandez, Francisco J | |
dc.contributor.author | Marin, Ana V | |
dc.contributor.author | Gomez, Sara | |
dc.contributor.author | Fulla, Daniel | |
dc.contributor.author | Melchor-Tafur, Cecilia | |
dc.contributor.author | Franco-Hidalgo, Virginia | |
dc.contributor.author | Albert, Sebastian | |
dc.contributor.author | Juanhuix, Jordi | |
dc.contributor.author | Rodriguez de Cordoba, Santiago | |
dc.contributor.author | Regueiro, Jose R | |
dc.contributor.author | Cristina Vega, M | |
dc.date.accessioned | 2024-07-11T09:07:45Z | |
dc.date.available | 2024-07-11T09:07:45Z | |
dc.date.issued | 2017-04-10 | |
dc.identifier.citation | 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. | en |
dc.identifier.issn | 1664-302X | |
dc.identifier.other | http://hdl.handle.net/20.500.13003/9868 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/20423 | |
dc.description.abstract | 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. | en |
dc.description.sponsorship | The research leading to these results has received funding from the Spanish Instituto de Salud Carlos III (PI12/01667 to CV), the Spanish Ministerio de Economia y Competitividad (CTQ2015-66206-C2-2-R and SAF2015-72961-EXP to CV, SAF2015-66287-R (MINECO/FEDER) to SR and SAF201454708-R to JR), CSIC (201620E064), the Regional Government of Madrid (S2010/BD-2316 to JR, CV, and SR), and the European Commission (Framework Programme 7 (FP7)) projects ComplexINC (Contract No. 279039 to CV) and EURenOmics (Contract No. 305608 to SR). AVM was supported by the Comunidad de Madrid (S2010/BMD-2316/2326) and the Universidad Complutense de Madrid (CT46/15). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | es_ES |
dc.language.iso | eng | en |
dc.publisher | Frontiers Media | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Anaphylatoxin | |
dc.subject | Chemoattraction | |
dc.subject | Complement system | |
dc.subject | C5a | |
dc.subject | GAPDH (glyceraldehyde-3-phosphate dehydrogenase) | |
dc.subject | gram-positive pathogen | |
dc.subject | Immunoevasion | |
dc.subject | x-ray crystallography | |
dc.title | 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 | en |
dc.type | research article | en |
dc.rights.license | Attribution 4.0 International | * |
dc.identifier.pubmedID | 28443070 | es_ES |
dc.format.volume | 8 | es_ES |
dc.format.page | 541 | es_ES |
dc.identifier.doi | 10.3389/fmicb.2017.00541 | |
dc.relation.publisherversion | https://dx.doi.org/10.3389/fmicb.2017.00541 | en |
dc.identifier.journal | Frontiers in Microbiology | es_ES |
dc.rights.accessRights | open access | en |
dc.identifier.scopus | 2-s2.0-85018291369 | |
dc.identifier.wos | 398656400001 | |
dc.identifier.pui | L615712534 |
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