000102201 001__ 102201
000102201 005__ 20230519145458.0
000102201 0247_ $$2doi$$a10.1016/j.jbc.2021.100307
000102201 0248_ $$2sideral$$a124257
000102201 037__ $$aART-2021-124257
000102201 041__ $$aeng
000102201 100__ $$aFurze, C.M.
000102201 245__ $$aStructural basis of trehalose recognition by the mycobacterial LpqY-SugABC transporter
000102201 260__ $$c2021
000102201 5060_ $$aAccess copy available to the general public$$fUnrestricted
000102201 5203_ $$aThe Mycobacterium tuberculosis (Mtb) LpqY-SugABC ATPbinding cassette transporter is a recycling system that imports trehalose released during remodeling of the Mtb cell-envelope. As this process is essential for the virulence of the Mtb pathogen, it may represent an important target for tuberculosis drug and diagnostic development, but the transporter specificity and molecular determinants of substrate recognition are unknown. To address this, we have determined the structural and biochemical basis of how mycobacteria transport trehalose using a combination of crystallography, saturation transfer difference NMR, molecular dynamics, site-directed mutagenesis, biochemical/biophysical assays, and the synthesis of trehalose analogs. This analysis pinpoints key residues of the LpqY substrate binding lipoprotein that dictate substratespecific recognition and has revealed which disaccharide modifications are tolerated. These findings provide critical insights into how the essential Mtb LpqY-SugABC transporter reuses trehalose and modified analogs and specifies a framework that can be exploited for the design of new antitubercular agents and/or diagnostic tools.
000102201 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000102201 590__ $$a5.485$$b2021
000102201 592__ $$a1.871$$b2021
000102201 594__ $$a8.8$$b2021
000102201 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b94 / 297 = 0.316$$c2021$$dQ2$$eT1
000102201 593__ $$aCell Biology$$c2021$$dQ1
000102201 593__ $$aBiochemistry$$c2021$$dQ1
000102201 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000102201 700__ $$0(orcid)0000-0001-8355-2289$$aDelso, I.$$uUniversidad de Zaragoza
000102201 700__ $$aCasal, E.
000102201 700__ $$aGuy, C.S.
000102201 700__ $$aSeddon, C.
000102201 700__ $$aBrown, C.M.
000102201 700__ $$aParker, H.L.
000102201 700__ $$aRadhakrishnan, A.
000102201 700__ $$aPacheco-Gomez, R.
000102201 700__ $$aStansfeld, P.J.
000102201 700__ $$aAngulo, J.
000102201 700__ $$aCameron, A.D.
000102201 700__ $$aFullam, E.
000102201 7102_ $$12013$$2765$$aUniversidad de Zaragoza$$bDpto. Química Orgánica$$cÁrea Química Orgánica
000102201 773__ $$g296, 100307 (2021), j.jbc.2021.100307 [12 pp]$$pJ. biol. chem.$$tJournal of Biological Chemistry$$x0021-9258
000102201 8564_ $$s2226107$$uhttps://zaguan.unizar.es/record/102201/files/texto_completo.pdf$$yVersión publicada
000102201 8564_ $$s3492183$$uhttps://zaguan.unizar.es/record/102201/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000102201 909CO $$ooai:zaguan.unizar.es:102201$$particulos$$pdriver
000102201 951__ $$a2023-05-18-14:52:59
000102201 980__ $$aARTICLE