PXD047943-1

PXD047943 is an original dataset announced via ProteomeXchange.

Title	Activity modulation in anaerobicribonucleotide reductases: nucleotidebinding: HDX-MS data
Description	A small, nucleotide-binding domain, the ATP-cone, is found at the N-terminus of mostribonucleotide reductase (RNR) catalytic subunits. By binding ATP or dATP it regulates theenzyme activity of all classes of RNR. Functional and structural work on aerobic RNRs hasrevealed a plethora of ways in which dATP inhibits activity by inducing oligomerization andpreventing a productive radical transfer from one subunit to the active site in the other.Anaerobic RNRs, on the other hand, store a stable glycyl radical next to the active site and thebasis for their dATP-dependent inhibition is completely unknown. We present biochemical,biophysical and structural information on the effects of ATP and dATP binding to theanaerobic RNR from Prevotella copri . The enzyme exists in a dimer-tetramer equilibriumbiased towards dimers when two ATP molecules are bound and tetramers when two dATPmolecules are bound. In the presence of ATP, P. copri NrdD is active and has a fully orderedglycyl radical domain (GRD) in one monomer of the dimer. Binding of dATP to the ATP-coneresults in loss of activity and disordering of the GRD. The glycyl radical is formed even in thedATP-bound form, but the substrate does not bind, suggesting that dATP inhibition inanaerobic RNRs acts by disordering of the GRD more than 30 Å away from the dATP molecule,thereby preventing both substrate binding and radical mobilisation. The structures implicatea complex network of activity regulation involving the GRD, the allosteric substratespecificity site and a conserved but previously unseen flap over the active site.
HostingRepository	PRIDE
AnnounceDate	2024-08-10
AnnouncementXML	Submission_2024-08-10_12:05:27.115.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simon Ekström
SpeciesList	scientific name: Prevotella corporis DSM 18810 = JCM 8529; NCBI TaxID: 1122981;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-19 05:29:47	ID requested
⏵ 1	2024-08-10 12:05:28	announced
2	2024-10-22 06:54:14	announced	2024-10-22: Updated project metadata.

Bimai O, Banerjee I, Rozman Grinberg I, Huang P, Hultgren L, Ekstr, ö, m S, Lundin D, Sj, ö, berg BM, Logan DT, Nucleotide binding to the ATP-cone in anaerobic ribonucleotide reductases allosterically regulates activity by modulating substrate binding. Elife, 12():(2024) [pubmed]

10.7554/elife.89292;

submitter keyword: anaerobicribonucleotide reductases, HDX-MS

Derek Logan
contact affiliation	Departmentof Biochemistry & Structural Biology Lund University, Sweden
contact email	derek.logan@biochemistry.lu.se
lab head
Simon Ekström
contact affiliation	BioMS - Swedish National Infrastructure for Biological Mass Spectrometry, Lund University, BMC D1330, 221 84 Lund, Sweden
contact email	simon.ekstrom@med.lu.se
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/08/PXD047943

PRIDE project URI

• PRIDE
  1. PXD047943
     1. Label: PRIDE project
     2. Name: Activity modulation in anaerobicribonucleotide reductases: nucleotidebinding: HDX-MS data