Journal Article

PUBDB-2025-01440

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Activity Regulation of a Glutamine Amidotransferase Bienzyme Complex by Substrate-Induced Subunit Interface Expansion

Funke, F. J. ; Schlee, S. ; Bento, I.Extern*EMBL* ; Bourenkov, G.XFEL.EU*EMBL* ; Sterner, R. (Corresponding author) ; Wilmanns, M. (Corresponding author)Extern*EMBL*

2025
ACS Washington, DC

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Please use a persistent id in citations: doi:10.1021/acscatal.4c07438  doi:10.3204/PUBDB-2025-01440

Abstract: Glutamine amidotransferases are multienzyme machineries in which reactive ammonia is generated by a glutaminase and then transferred through a sequestered protein tunnel to a synthase active site for incorporation into diverse metabolites. To avoid wasteful metabolite consumption, there is a requirement for synchronized catalysis, but any generally applicable mechanistic insight is still lacking. As synthase activity depends on glutamine turnover, we investigated possible mechanisms controlling glutaminase catalysis using aminodeoxychorismate synthase involved in folate biosynthesis as a model. By analyzing this system in distinct states of catalysis, we found that incubation with glutamine leads to a subunit interface expansion by one-third of its original area. These changes completely enclose the glutaminase active site for sequestered catalysis and the subsequent transport of volatile ammonia to the synthase active site. In view of similar rearrangements in other glutamine amidotransferases, our observations may provide a general mechanism for the catalysis synchronization of this multienzyme family.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)
2. EMBL (EMBL)
3. CSSB-CF-SPC (CSSB-CF-SPC)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)

Experiment(s):

1. PETRA Beamline P13 (PETRA III)

Appears in the scientific report 2025

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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