2.6-Å resolution cryo-EM structure of a class Ia ribonucleotide reductase trapped with mechanism-based inhibitor N

Cryoelectron Microscopy / methods Ribonucleotide Reductases / chemistry Escherichia coli / enzymology Catalytic Domain Cytidine Diphosphate / chemistry Models, Molecular Enzyme Inhibitors / chemistry Escherichia coli Proteins / chemistry
cryogenic electron microscopy enzyme inhibition proton-coupled electron transfer radical chemistry

Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
05 Nov 2024
Historique:
medline: 30 10 2024
pubmed: 30 10 2024
entrez: 30 10 2024
Statut: ppublish

Résumé

Ribonucleotide reductases (RNRs) reduce ribonucleotides to deoxyribonucleotides using radical-based chemistry. For class Ia RNRs, the radical species is stored in a separate subunit (β2) from the subunit housing the active site (α2), requiring the formation of a short-lived α2β2 complex and long-range radical transfer (RT). RT occurs via proton-coupled electron transfer (PCET) over a long distance (~32-Å) and involves the formation and decay of multiple amino acid radical species. Here, we use cryogenic electron microscopy and a mechanism-based inhibitor 2'-azido-2'-deoxycytidine-5'-diphosphate (N

Identifiants

DOI: 10.1073/pnas.2417157121 PMID: 39475643
pubmed: 39475643
doi: 10.1073/pnas.2417157121
doi:

Substances chimiques

Ribonucleotide Reductases EC 1.17.4.-
Cytidine Diphosphate 63-38-7
Enzyme Inhibitors 0
Escherichia coli Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2417157121

Subventions

Organisme : HHS | NIH | National Institute of General Medical Sciences (NIGMS)
ID : GM126982
Organisme : HHS | NIH | National Institute of General Medical Sciences (NIGMS)
ID : GM047274
Organisme : HHS | NIH | National Institute of General Medical Sciences (NIGMS)
ID : GM29595
Organisme : NIGMS NIH HHS
ID : F32 GM145072
Pays : United States
Organisme : Howard Hughes Medical Institute (HHMI)
ID : Investigator

Déclaration de conflit d'intérêts

Competing interests statement:The authors declare no competing interest.

Auteurs

Dana E Westmoreland (DE)

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.

Patricia R Feliciano (PR)

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
HHMI, Massachusetts Institute of Technology, Cambridge, MA 02139.
ORCID: 0000-0003-3853-115X

Gyunghoon Kang (G)

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
HHMI, Massachusetts Institute of Technology, Cambridge, MA 02139.
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.

Chang Cui (C)

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138.

Albert Kim (A)

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.

JoAnne Stubbe (J)

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
ORCID: 0000-0001-8076-4489

Daniel G Nocera (DG)

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138.
ORCID: 0000-0001-5055-320X

Catherine L Drennan (CL)

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
HHMI, Massachusetts Institute of Technology, Cambridge, MA 02139.
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
ORCID: 0000-0001-5486-2755

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Classifications MeSH

questionsmedicales.fr › Techniques d'investigation › Microscopie électronique › Cryomicroscopie électronique › 2.6-Å resolution cryo-EM structure of a class...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Ribonucleotide reductases › 2.6-Å resolution cryo-EM structure of a class...
questionsmedicales.fr › Bactéries › Proteobacteria › Gammaproteobacteria › Enterobacteriaceae › Escherichia › Escherichia coli › 2.6-Å resolution cryo-EM structure of a class...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Éléments structuraux des protéines › Domaine catalytique › 2.6-Å resolution cryo-EM structure of a class...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Ribonucléotides › Nucléotides cytidyliques › Cytidine diphosphate › 2.6-Å resolution cryo-EM structure of a class...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › 2.6-Å resolution cryo-EM structure of a class...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › 2.6-Å resolution cryo-EM structure of a class...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines bactériennes › Protéines Escherichia coli › 2.6-Å resolution cryo-EM structure of a class...