000148928 001__ 148928
000148928 005__ 20250123152145.0
000148928 0247_ $$2doi$$a10.1016/j.abb.2025.110288
000148928 0248_ $$2sideral$$a142107
000148928 037__ $$aART-2025-142107
000148928 041__ $$aeng
000148928 100__ $$0(orcid)0000-0001-7947-8813$$aMinjárez-Sáenz, Martha
000148928 245__ $$aStructural and functional insights into UDP-N-acetylglucosamine-enolpyruvate reductase (MurB) from Brucella ovis
000148928 260__ $$c2025
000148928 5203_ $$aThe peptidoglycan biosynthetic pathway involves a series of enzymatic reactions in which UDP-N-acetylglucosamine-enolpyruvate reductase (MurB) plays a crucial role in catalyzing the conversion of UDP-N-acetylglucosamine-enolpyruvate (UNAGEP) to UDP-N-acetylmuramic acid. This reaction relies on NADPH and FAD and, since MurB is not found in eukaryotes, it is an attractive target for the development of antimicrobials. MurB from Brucella ovis, the causative agent of brucellosis in sheep, is characterized here. The FAD cofactor in MurB of B. ovis is reduced to the hydroquinone state without semiquinone stabilization with an estimated Eox/hq of −260 mV. MurB from B. ovis catalyzes the oxidation of NADPH in a slow process that is positively influenced by the presence of the second product, UNAGEP. The crystallographic structure of the MurBox:UNAGEP complex confirms its folding into three domains and the binding of UNAGEP, positioning its enolpyruvyl group for hydride transfer from FAD. MurB shows a complex thermal unfolding pathway that is influenced by UNAGEP and NADP+, confirming its ability to bind both molecules. Molecular dynamics (MD) simulations predict that the nicotinamide of NADP+ is more stable at the active site than the enolpyruvyl of UNAGEP, and suggests that MurB can simultaneously accommodate NADPH and UNAGEP in the substrate channel, increasing overall protein-ligand flexibility. Sequence and evolutionary analyses show that MurB from B. ovis conserves all motifs predicted to be involved in catalysis within the Type IIa family.
000148928 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E35-23R$$9info:eu-repo/grantAgreement/ES/DGA/LMP13_21$$9info:eu-repo/grantAgreement/ES/MICINN/PID2022-136369NB-I00
000148928 540__ $$9info:eu-repo/semantics/closedAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000148928 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000148928 700__ $$aRivero, Maribel$$uUniversidad de Zaragoza
000148928 700__ $$aCorrea-Pérez, Víctor$$uUniversidad de Zaragoza
000148928 700__ $$aBoneta, Sergio
000148928 700__ $$aSuárez, Paula
000148928 700__ $$0(orcid)0000-0001-5823-7965$$aPolo, Víctor$$uUniversidad de Zaragoza
000148928 700__ $$aSadeghi, Sheila J.
000148928 700__ $$0(orcid)0000-0003-3608-4720$$aYruela, Inmaculada
000148928 700__ $$0(orcid)0000-0001-9047-0046$$aMartínez-Júlvez, Marta$$uUniversidad de Zaragoza
000148928 700__ $$0(orcid)0000-0001-8743-0182$$aMedina, Milagros$$uUniversidad de Zaragoza
000148928 7102_ $$12012$$2755$$aUniversidad de Zaragoza$$bDpto. Química Física$$cÁrea Química Física
000148928 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000148928 773__ $$g765 (2025), 110288 [19 pp.]$$pArch. biochem. biophys.$$tARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS$$x0003-9861
000148928 8564_ $$s12381399$$uhttps://zaguan.unizar.es/record/148928/files/texto_completo.pdf$$yVersión publicada$$zinfo:eu-repo/date/embargoEnd/2026-01-04
000148928 8564_ $$s2477272$$uhttps://zaguan.unizar.es/record/148928/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada$$zinfo:eu-repo/date/embargoEnd/2026-01-04
000148928 909CO $$ooai:zaguan.unizar.es:148928$$particulos$$pdriver
000148928 951__ $$a2025-01-23-14:47:15
000148928 980__ $$aARTICLE