A nucleotide-switch mechanism mediates opposing catalytic activities of Rel enzymes

Tamman, Hedvig (author)

Van Nerom, Katleen (author)

Takada, Hiraku (author): Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Molekylär Infektionsmedicin, Sverige (MIMS)

Vandenberk, Niels (author)

Scholls, Daniel (author)

Polikanov, Yury (author)

Hofkens, Johan (author)

Talavera, Ariel (author)

Hauryliuk, Vasili, 1980- (author): Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Molekylär Infektionsmedicin, Sverige (MIMS)

Hendrix, Jelle (author)

Garcia-Pino, Abel (author)

(creator_code:org_t)

2020-05-11
2020
English.
In: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 16:8, s. 834-840

Related links:: https://doi.org/10.1...; show more...; https://umu.diva-por... (primary) (Raw object); http://umu.diva-port...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

Bifunctional Rel stringent factors, the most abundant class of RelA/SpoT homologs, are ribosome-associated enzymes that transfer a pyrophosphate from ATP onto the 3 ' of guanosine tri-/diphosphate (GTP/GDP) to synthesize the bacterial alarmone (p)ppGpp, and also catalyze the 3 ' pyrophosphate hydrolysis to degrade it. The regulation of the opposing activities of Rel enzymes is a complex allosteric mechanism that remains an active research topic despite decades of research. We show that a guanine-nucleotide-switch mechanism controls catalysis by Thermus thermophilus Rel (Rel(Tt)). The binding of GDP/ATP opens the N-terminal catalytic domains (NTD) of Rel(Tt) (Rel(Tt)(NTD)) by stretching apart the two catalytic domains. This activates the synthetase domain and allosterically blocks hydrolysis. Conversely, binding of ppGpp to the hydrolase domain closes the NTD, burying the synthetase active site and precluding the binding of synthesis precursors. This allosteric mechanism is an activity switch that safeguards against futile cycles of alarmone synthesis and degradation.

By the author/editor: Tamman, Hedvig; Van Nerom, Katle ...; Takada, Hiraku; Vandenberk, Niel ...; Scholls, Daniel; Polikanov, Yury; show more...; Hofkens, Johan; Talavera, Ariel; Hauryliuk, Vasil ...; Hendrix, Jelle; Garcia-Pino, Abe ...; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

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