Journal article Closed Access
Marco De Vivo; Marco De Vivo; Emiliano Ippoliti; Vito Genna; Vito Genna; Paolo Carloni; Pietro Vidossich
{ "conceptrecid": "91730", "created": "2023-09-25T01:50:16.494994+00:00", "doi": "10.1021/jacs.6b05475", "id": 91731, "links": { "badge": "https://www.openaccessrepository.it/badge/doi/10.1021/jacs.6b05475.svg", "doi": "https://doi.org/10.1021/jacs.6b05475", "html": "https://www.openaccessrepository.it/record/91731", "latest": "https://www.openaccessrepository.it/api/records/91731", "latest_html": "https://www.openaccessrepository.it/record/91731" }, "metadata": { "access_right": "closed", "access_right_category": "danger", "communities": [ { "id": "itmirror" } ], "creators": [ { "name": "Marco De Vivo" }, { "name": "Marco De Vivo" }, { "name": "Emiliano Ippoliti" }, { "name": "Vito Genna" }, { "name": "Vito Genna" }, { "name": "Paolo Carloni" }, { "name": "Pietro Vidossich" } ], "description": "The enzymatic polymerization of DNA and RNA is the basis for genetic inheritance for all living organisms. It is catalyzed by the DNA/RNA polymerase (Pol) superfamily. Here, bioinformatics analysis reveals that the incoming nucleotide substrate always forms an H-bond between its 3\u2032-OH and \u03b2-phosphate moieties upon formation of the Michaelis complex. This previously unrecognized H-bond implies a novel self-activated mechanism (SAM), which synergistically connects the in situ nucleophile formation with subsequent nucleotide addition and, importantly, nucleic acid translocation. Thus, SAM allows an elegant and efficient closed-loop sequence of chemical and physical steps for Pol catalysis. This is markedly different from previous mechanistic hypotheses. Our proposed mechanism is corroborated via ab initio QM/MM simulations on a specific Pol, the human DNA polymerase-\u03b7, an enzyme involved in repairing damaged DNA. The structural conservation of DNA and RNA Pols supports the possible extension of SAM to Pol enzymes from the three domains of life.", "doi": "10.1021/jacs.6b05475", "keywords": [ "Colloid and Surface Chemistry", "Biochemistry", "General Chemistry", "Catalysis" ], "language": "eng", "license": { "id": "other-open" }, "notes": "", "publication_date": "2016-08-31", "relations": { "version": [ { "count": 1, "index": 0, "is_last": true, "last_child": { "pid_type": "recid", "pid_value": "91731" }, "parent": { "pid_type": "recid", "pid_value": "91730" } } ] }, "resource_type": { "subtype": "article", "title": "Journal article", "type": "publication" }, "title": "A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases" }, "owners": [ 14 ], "revision": 1, "stats": { "downloads": 0.0, "unique_downloads": 0.0, "unique_views": 0.0, "version_downloads": 0.0, "version_unique_downloads": 0.0, "version_unique_views": 0.0, "version_views": 0.0, "version_volume": 0.0, "views": 0.0, "volume": 0.0 }, "updated": "2023-09-25T01:50:16.567267+00:00" }
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