Introducing a New Bond-Forming Activity in an Archaeal DNA Polymerase by Structure-Guided Enzyme Redesign.

Catalytic Domain DNA / chemistry DNA Replication DNA, Archaeal DNA-Directed DNA Polymerase / metabolism

Journal

ACS chemical biology
ISSN: 1554-8937
Titre abrégé: ACS Chem Biol
Pays: United States
ID NLM: 101282906

Informations de publication

Date de publication:
15 07 2022
Historique:
pubmed: 2 7 2022
medline: 19 7 2022
entrez: 1 7 2022
Statut: ppublish

Résumé

DNA polymerases have evolved to feature a highly conserved activity across the tree of life: formation of, without exception, internucleotidyl O-P linkages. Can this linkage selectivity be overcome by design to produce xenonucleic acids? Here, we report that the structure-guided redesign of an archaeal DNA polymerase, 9°N, exhibits a new activity undetectable in the wild-type enzyme: catalyzing the formation of internucleotidyl N-P linkages using 3'-NH

Identifiants

DOI: 10.1021/acschembio.2c00373 PMID: 35776893 PMC: PMC9442636
pubmed: 35776893
doi: 10.1021/acschembio.2c00373
pmc: PMC9442636
mid: NIHMS1823491
doi:

Substances chimiques

DNA, Archaeal 0
DNA 9007-49-2
DNA-Directed DNA Polymerase EC 2.7.7.7

Types de publication

Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1924-1936

Subventions

Organisme : NCI NIH HHS
ID : P30 CA072720
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM107485
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM132565
Pays : United States
Organisme : NIBIB NIH HHS
ID : R21 EB029548
Pays : United States

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Auteurs

Tushar Aggarwal (T)

Department of Chemistry and Chemical Biology, Rutgers University, New Brunswick, New Jersey 08854, United States.
ORCID: 0000-0002-6641-0964

William A Hansen (WA)

Institute for Quantitative Biomedicine, Rutgers University, New Brunswick, New Jersey 08854, United States.

Jonathan Hong (J)

Department of Chemistry and Chemical Biology, Rutgers University, New Brunswick, New Jersey 08854, United States.

Abir Ganguly (A)

Institute for Quantitative Biomedicine, Rutgers University, New Brunswick, New Jersey 08854, United States.
Laboratory for Biomolecular Simulation Research, Rutgers University, New Brunswick, New Jersey 08854, United States.
ORCID: 0000-0002-0630-1109

Darrin M York (DM)

Department of Chemistry and Chemical Biology, Rutgers University, New Brunswick, New Jersey 08854, United States.
Institute for Quantitative Biomedicine, Rutgers University, New Brunswick, New Jersey 08854, United States.
Laboratory for Biomolecular Simulation Research, Rutgers University, New Brunswick, New Jersey 08854, United States.
Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey 08901, United States.
ORCID: 0000-0002-9193-7055

Sagar D Khare (SD)

Department of Chemistry and Chemical Biology, Rutgers University, New Brunswick, New Jersey 08854, United States.
Institute for Quantitative Biomedicine, Rutgers University, New Brunswick, New Jersey 08854, United States.
Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey 08901, United States.

Enver Cagri Izgu (EC)

Department of Chemistry and Chemical Biology, Rutgers University, New Brunswick, New Jersey 08854, United States.
Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey 08901, United States.
Rutgers Center for Lipid Research and New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, New Jersey 08901, United States.
ORCID: 0000-0001-6673-3635

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Classifications MeSH

questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Éléments structuraux des protéines › Domaine catalytique › Introducing a New Bond-Forming Activity in an...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › Introducing a New Bond-Forming Activity in an...
questionsmedicales.fr › Phénomènes génétiques › Réplication de l'ADN › Introducing a New Bond-Forming Activity in an...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › ADN des archées › Introducing a New Bond-Forming Activity in an...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Nucleotidyltransferases › DNA nucleotidyltransferases › DNA-directed DNA polymerase › Introducing a New Bond-Forming Activity in an...