000646213 001__ 646213
000646213 005__ 20260217210828.0
000646213 0247_ $$2doi$$a10.1080/21505594.2025.2609393
000646213 0247_ $$2ISSN$$a2150-5594
000646213 0247_ $$2ISSN$$a2150-5608
000646213 0247_ $$2datacite_doi$$a10.3204/PUBDB-2026-00758
000646213 037__ $$aPUBDB-2026-00758
000646213 041__ $$aEnglish
000646213 082__ $$a610
000646213 1001_ $$00009-0002-3996-7166$$aSchütt, Isabell$$b0
000646213 245__ $$aInhibitors of GapN-dependent NADPH supply as potential lead compounds for novel therapeutics against Streptococcus pyogenes
000646213 260__ $$aAustin, Tex.$$bLandes Bioscience$$c2026
000646213 3367_ $$2DRIVER$$aarticle
000646213 3367_ $$2DataCite$$aOutput Types/Journal article
000646213 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1771330836_907078
000646213 3367_ $$2BibTeX$$aARTICLE
000646213 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000646213 3367_ $$00$$2EndNote$$aJournal Article
000646213 520__ $$aInfections with Streptococcus pyogenes are among the most important diseases caused by bacteria and are responsible for around 500,000 deaths every year. In 2024, macrolide-resistant S. pyogenes was added to the WHO’s list of priority pathogens. The non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase GapN has been identified as a potential drug target in S. pyogenes. SpyGapN is the major NADP-reducing enzyme in these bacteria as they lack the oxidative part of the pentose phosphate pathway. In this study, in silico docking of compound libraries to the glyceraldehyde 3-phosphate binding pocket of SpyGapN was used to screen for potential competitive inhibitors. Among the candidates identified with this approach, 1,2-dihydroxyethane-1,2-disulfonate (glyoxal bisulfite) showed the strongest inhibition of SpyGapN activity in vitro. In a complementary approach, crystallographic fragment screening was conducted, which identified the ultra-low-molecular-weight compounds pyrimidine-5-amine and 4-hydroxypyridazine targeting the cofactor-binding pocket of SpyGapN. Both low-molecular-weight compounds were experimentally confirmed to inhibit the activity of purified SpyGapN. Combinations of glyoxal bisulfite with either pyrimidine-5-amine or 4-hydroxypyridazine enhanced the inhibitory effect of SpyGapN. Glyoxal bisulfite was able to kill S. pyogenes. This effect was accelerated by combining glyoxal bisulfite with 4-hydroxypyridazine. While these findings suggest that inhibition of SpyGapN probably contributes to the observed antibacterial activity, the exact mechanism of action remains to be confirmed, as the compounds also affect other G3P-converting enzymes. Nevertheless, these compounds provide a promising starting point for the development of more specific SpyGapN inhibitors.
000646213 536__ $$0G:(DE-HGF)POF4-6G3$$a6G3 - PETRA III (DESY) (POF4-6G3)$$cPOF4-6G3$$fPOF IV$$x0
000646213 588__ $$aDataset connected to CrossRef, Journals: bib-pubdb1.desy.de
000646213 693__ $$0EXP:(DE-H253)P-P13-20150101$$1EXP:(DE-H253)PETRAIII-20150101$$6EXP:(DE-H253)P-P13-20150101$$aPETRA III$$fPETRA Beamline P13$$x0
000646213 7001_ $$aEinwohlt, Philip$$b1
000646213 7001_ $$aWandinger, Anna-Maria$$b2
000646213 7001_ $$aTeuffel, Jonathan$$b3
000646213 7001_ $$aWirsing, Regina$$b4
000646213 7001_ $$aHlawatschke, Ben H.$$b5
000646213 7001_ $$aFehlauer, Hanna L.$$b6
000646213 7001_ $$aBothe, Sebastian$$b7
000646213 7001_ $$aBader, Nicole$$b8
000646213 7001_ $$aMonaci, Emanuele$$b9
000646213 7001_ $$00000-0001-9527-5098$$aKreikemeyer, Bernd$$b10
000646213 7001_ $$aSchindelin, Hermann$$b11
000646213 7001_ $$aWade, Rebecca C.$$b12
000646213 7001_ $$0P:(DE-HGF)0$$aFiedler, Tomas$$b13$$eCorresponding author
000646213 773__ $$0PERI:(DE-600)2657572-3$$a10.1080/21505594.2025.2609393$$gVol. 17, no. 1, p. 2609393$$n1$$p2609393$$tVirulence$$v17$$x2150-5594$$y2026
000646213 8564_ $$uhttps://www.tandfonline.com/doi/full/10.1080/21505594.2025.2609393#d1e551
000646213 8564_ $$uhttps://bib-pubdb1.desy.de/record/646213/files/Inhibitors%20of%20GapN-dependent%20NADPH%20supply%20as%20potential%20lead%20compounds%20for%20novel%20therapeutics%20against%20Streptococcus%20pyogenes.pdf$$yOpenAccess
000646213 8564_ $$uhttps://bib-pubdb1.desy.de/record/646213/files/Inhibitors%20of%20GapN-dependent%20NADPH%20supply%20as%20potential%20lead%20compounds%20for%20novel%20therapeutics%20against%20Streptococcus%20pyogenes.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000646213 909CO $$ooai:bib-pubdb1.desy.de:646213$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery
000646213 9131_ $$0G:(DE-HGF)POF4-6G3$$1G:(DE-HGF)POF4-6G0$$2G:(DE-HGF)POF4-600$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bForschungsbereich Materie$$lGroßgeräte: Materie$$vPETRA III (DESY)$$x0
000646213 9141_ $$y2026
000646213 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2025-11-11
000646213 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2025-11-11
000646213 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2025-11-11
000646213 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2025-11-11
000646213 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2025-11-11
000646213 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bVIRULENCE : 2022$$d2025-11-11
000646213 915__ $$0LIC:(DE-HGF)CCBYNC4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial CC BY-NC 4.0
000646213 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2024-08-08T20:19:27Z
000646213 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2024-08-08T20:19:27Z
000646213 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2025-11-11
000646213 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2025-11-11
000646213 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2025-11-11
000646213 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000646213 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2025-11-11
000646213 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2025-11-11
000646213 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bVIRULENCE : 2022$$d2025-11-11
000646213 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2025-11-11
000646213 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2025-11-11
000646213 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2025-11-11
000646213 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2025-11-11
000646213 9201_ $$0I:(DE-H253)EMBL-User-20120814$$kEMBL-User$$lEMBL-User$$x0
000646213 980__ $$ajournal
000646213 980__ $$aVDB
000646213 980__ $$aUNRESTRICTED
000646213 980__ $$aI:(DE-H253)EMBL-User-20120814
000646213 9801_ $$aFullTexts