000099687 001__ 99687
000099687 005__ 20230519145418.0
000099687 0247_ $$2doi$$a10.1038/s41467-021-21165-9
000099687 0248_ $$2sideral$$a123126
000099687 037__ $$aART-2021-123126
000099687 041__ $$aeng
000099687 100__ $$aBellin, L.
000099687 245__ $$aMechanisms of feedback inhibition and sequential firing of active sites in plant aspartate transcarbamoylase
000099687 260__ $$c2021
000099687 5060_ $$aAccess copy available to the general public$$fUnrestricted
000099687 5203_ $$aAspartate transcarbamoylase (ATC), an essential enzyme for de novo pyrimidine biosynthesis, is uniquely regulated in plants by feedback inhibition of uridine 5-monophosphate (UMP). Despite its importance in plant growth, the structure of this UMP-controlled ATC and the regulatory mechanism remain unknown. Here, we report the crystal structures of Arabidopsis ATC trimer free and bound to UMP, complexed to a transition-state analog or bearing a mutation that turns the enzyme insensitive to UMP. We found that UMP binds and blocks the ATC active site, directly competing with the binding of the substrates. We also prove that UMP recognition relies on a loop exclusively conserved in plants that is also responsible for the sequential firing of the active sites. In this work, we describe unique regulatory and catalytic properties of plant ATCs that could be exploited to modulate de novo pyrimidine synthesis and plant growth.
000099687 536__ $$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BFU2016-80570-R$$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/RTI2018-098084-B-100
000099687 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000099687 590__ $$a17.694$$b2021
000099687 592__ $$a4.846$$b2021
000099687 594__ $$a23.2$$b2021
000099687 591__ $$aMULTIDISCIPLINARY SCIENCES$$b6 / 74 = 0.081$$c2021$$dQ1$$eT1
000099687 593__ $$aChemistry (miscellaneous)$$c2021$$dQ1
000099687 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2021$$dQ1
000099687 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000099687 700__ $$aDel Caño-Ochoa, F.
000099687 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, A.$$uUniversidad de Zaragoza
000099687 700__ $$aMöhlmann, T.
000099687 700__ $$aRamón-Maiques, S.
000099687 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000099687 773__ $$g12, 1 (2021), 947 [11 pp]$$tNature communications$$x2041-1723
000099687 8564_ $$s1454850$$uhttps://zaguan.unizar.es/record/99687/files/texto_completo.pdf$$yVersión publicada
000099687 8564_ $$s1565586$$uhttps://zaguan.unizar.es/record/99687/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000099687 909CO $$ooai:zaguan.unizar.es:99687$$particulos$$pdriver
000099687 951__ $$a2023-05-18-14:04:22
000099687 980__ $$aARTICLE