Role of allosteric switches and adaptor domains in long-distance cross-talk and transient tunnel formation.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
18
07
2019
accepted:
08
01
2020
entrez:
15
4
2020
pubmed:
15
4
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Transient tunnels that assemble and disassemble to facilitate passage of unstable intermediates in enzymes containing multiple reaction centers are controlled by allosteric cues. Using the 140-kDa purine biosynthetic enzyme PurL as a model system and a combination of biochemical and x-ray crystallographic studies, we show that long-distance communication between ~25-Å distal active sites is initiated by an allosteric switch, residing in a conserved catalytic loop, adjacent to the synthetase active site. Further, combinatory experiments seeded from molecular dynamics simulations help to delineate transient states that bring out the central role of nonfunctional adaptor domains. We show that carefully orchestrated conformational changes, facilitated by interplay of dynamic interactions at the allosteric switch and adaptor-domain interface, control reactivity and concomitant formation of the ammonia tunnel. This study asserts that substrate channeling is modulated by allosteric hotspots that alter protein energy landscape, thereby allowing the protein to adopt transient conformations paramount to function.
Identifiants
pubmed: 32284973
doi: 10.1126/sciadv.aay7919
pii: aay7919
pmc: PMC7124931
doi:
Substances chimiques
Proteins
0
Ammonia
7664-41-7
Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor
EC 6.3.5.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
eaay7919Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
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