Reaction mechanism of nucleoside 2’-deoxyribosyltransferases: free-energy landscape supports an oxocarbenium ion as the reaction intermediate
Insight into the catalytic mechanism of Lactobacillus leichmannii nucleoside 2′-deoxyribosyltransferase (LlNDT) has been gained by calculating a quantum mechanics–molecular mechanics (QM/MM) free-energy landscape of the reaction within the enzyme active site. Our results support an oxocarbenium spec...
- Autores:
-
Del Arco, Jon
Perona Requena, Almudena
González, Leticia
Fernández Lucas, Jesús
Gago, Federico
Sánchez-Murcia, Pedro Alejandro
- Tipo de recurso:
- http://purl.org/coar/resource_type/c_816b
- Fecha de publicación:
- 2019
- Institución:
- Corporación Universidad de la Costa
- Repositorio:
- REDICUC - Repositorio CUC
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.cuc.edu.co:11323/5253
- Acceso en línea:
- https://hdl.handle.net/11323/5253
https://repositorio.cuc.edu.co/
- Palabra clave:
- Nucleoside 2’-deoxyribosyltransferases
Oxocarbenium ion
Reaction intermediate
- Rights
- openAccess
- License
- CC0 1.0 Universal
| id |
RCUC2_ffd2a5ec36b0ae64ca97c7ea938cf83e |
|---|---|
| oai_identifier_str |
oai:repositorio.cuc.edu.co:11323/5253 |
| network_acronym_str |
RCUC2 |
| network_name_str |
REDICUC - Repositorio CUC |
| repository_id_str |
|
| dc.title.spa.fl_str_mv |
Reaction mechanism of nucleoside 2’-deoxyribosyltransferases: free-energy landscape supports an oxocarbenium ion as the reaction intermediate |
| title |
Reaction mechanism of nucleoside 2’-deoxyribosyltransferases: free-energy landscape supports an oxocarbenium ion as the reaction intermediate |
| spellingShingle |
Reaction mechanism of nucleoside 2’-deoxyribosyltransferases: free-energy landscape supports an oxocarbenium ion as the reaction intermediate Nucleoside 2’-deoxyribosyltransferases Oxocarbenium ion Reaction intermediate |
| title_short |
Reaction mechanism of nucleoside 2’-deoxyribosyltransferases: free-energy landscape supports an oxocarbenium ion as the reaction intermediate |
| title_full |
Reaction mechanism of nucleoside 2’-deoxyribosyltransferases: free-energy landscape supports an oxocarbenium ion as the reaction intermediate |
| title_fullStr |
Reaction mechanism of nucleoside 2’-deoxyribosyltransferases: free-energy landscape supports an oxocarbenium ion as the reaction intermediate |
| title_full_unstemmed |
Reaction mechanism of nucleoside 2’-deoxyribosyltransferases: free-energy landscape supports an oxocarbenium ion as the reaction intermediate |
| title_sort |
Reaction mechanism of nucleoside 2’-deoxyribosyltransferases: free-energy landscape supports an oxocarbenium ion as the reaction intermediate |
| dc.creator.fl_str_mv |
Del Arco, Jon Perona Requena, Almudena González, Leticia Fernández Lucas, Jesús Gago, Federico Sánchez-Murcia, Pedro Alejandro |
| dc.contributor.author.spa.fl_str_mv |
Del Arco, Jon Perona Requena, Almudena González, Leticia Fernández Lucas, Jesús Gago, Federico Sánchez-Murcia, Pedro Alejandro |
| dc.subject.spa.fl_str_mv |
Nucleoside 2’-deoxyribosyltransferases Oxocarbenium ion Reaction intermediate |
| topic |
Nucleoside 2’-deoxyribosyltransferases Oxocarbenium ion Reaction intermediate |
| description |
Insight into the catalytic mechanism of Lactobacillus leichmannii nucleoside 2′-deoxyribosyltransferase (LlNDT) has been gained by calculating a quantum mechanics–molecular mechanics (QM/MM) free-energy landscape of the reaction within the enzyme active site. Our results support an oxocarbenium species as the reaction intermediate and thus an SN1 reaction mechanism in this family of bacterial enzymes. Our mechanistic proposal is validated by comparing experimental kinetic data on the impact of the single amino acid replacements Tyr7, Glu98 and Met125 with Ala, Asp and Ala/norLeu, respectively, and accounts for the specificity shown by this enzyme on a non-natural substrate. This work broadens our understanding of enzymatic C–N bond cleavage and C–N bond formation. |
| publishDate |
2019 |
| dc.date.accessioned.none.fl_str_mv |
2019-09-11T15:27:46Z |
| dc.date.available.none.fl_str_mv |
2019-09-11T15:27:46Z |
| dc.date.issued.none.fl_str_mv |
2019 |
| dc.type.spa.fl_str_mv |
Pre-Publicación |
| dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_816b |
| dc.type.content.spa.fl_str_mv |
Text |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/preprint |
| dc.type.redcol.spa.fl_str_mv |
http://purl.org/redcol/resource_type/ARTOTR |
| dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/acceptedVersion |
| format |
http://purl.org/coar/resource_type/c_816b |
| status_str |
acceptedVersion |
| dc.identifier.uri.spa.fl_str_mv |
https://hdl.handle.net/11323/5253 |
| dc.identifier.instname.spa.fl_str_mv |
Corporación Universidad de la Costa |
| dc.identifier.reponame.spa.fl_str_mv |
REDICUC - Repositorio CUC |
| dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.cuc.edu.co/ |
| url |
https://hdl.handle.net/11323/5253 https://repositorio.cuc.edu.co/ |
| identifier_str_mv |
Corporación Universidad de la Costa REDICUC - Repositorio CUC |
| dc.language.iso.none.fl_str_mv |
spa |
| language |
spa |
| dc.rights.spa.fl_str_mv |
CC0 1.0 Universal |
| dc.rights.uri.spa.fl_str_mv |
http://creativecommons.org/publicdomain/zero/1.0/ |
| dc.rights.accessrights.spa.fl_str_mv |
info:eu-repo/semantics/openAccess |
| dc.rights.coar.spa.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
| rights_invalid_str_mv |
CC0 1.0 Universal http://creativecommons.org/publicdomain/zero/1.0/ http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.publisher.spa.fl_str_mv |
Universidad de la Costa |
| institution |
Corporación Universidad de la Costa |
| bitstream.url.fl_str_mv |
https://repositorio.cuc.edu.co/bitstreams/509421b9-1ab9-45bb-93d9-6578d78f21ae/download https://repositorio.cuc.edu.co/bitstreams/76acbfbe-fd34-4422-8cb9-69e16bb6050b/download https://repositorio.cuc.edu.co/bitstreams/72a2e534-6525-489e-a8c2-5dd7fcf013bd/download https://repositorio.cuc.edu.co/bitstreams/5f282022-a5f5-47c0-8a9c-ab63c27a73f2/download https://repositorio.cuc.edu.co/bitstreams/a2076520-4d42-4fb5-a5dc-a3e47968a9a0/download https://repositorio.cuc.edu.co/bitstreams/f13bd0cc-a229-4240-a0b7-223b0dedc5c6/download |
| bitstream.checksum.fl_str_mv |
9a12121cfa0c2ba0d7431489944b458d 42fd4ad1e89814f5e4a476b409eb708c 8a4605be74aa9ea9d79846c1fba20a33 730613039be56a20b9ea9e41cccfb32b 290ef00377d85d316a30d0665b5dd6c6 1c5539e7e710ee39388f083a020fa4d1 |
| bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 MD5 |
| repository.name.fl_str_mv |
Repositorio de la Universidad de la Costa CUC |
| repository.mail.fl_str_mv |
repdigital@cuc.edu.co |
| _version_ |
1811760716747636736 |
| spelling |
Del Arco, JonPerona Requena, AlmudenaGonzález, LeticiaFernández Lucas, JesúsGago, FedericoSánchez-Murcia, Pedro Alejandro2019-09-11T15:27:46Z2019-09-11T15:27:46Z2019https://hdl.handle.net/11323/5253Corporación Universidad de la CostaREDICUC - Repositorio CUChttps://repositorio.cuc.edu.co/Insight into the catalytic mechanism of Lactobacillus leichmannii nucleoside 2′-deoxyribosyltransferase (LlNDT) has been gained by calculating a quantum mechanics–molecular mechanics (QM/MM) free-energy landscape of the reaction within the enzyme active site. Our results support an oxocarbenium species as the reaction intermediate and thus an SN1 reaction mechanism in this family of bacterial enzymes. Our mechanistic proposal is validated by comparing experimental kinetic data on the impact of the single amino acid replacements Tyr7, Glu98 and Met125 with Ala, Asp and Ala/norLeu, respectively, and accounts for the specificity shown by this enzyme on a non-natural substrate. This work broadens our understanding of enzymatic C–N bond cleavage and C–N bond formation.Del Arco, Jon-will be generated-orcid-0000-0003-4646-492X-600Perona Requena, Almudena-will be generated-orcid-0000-0002-2402-4926-600González, LeticiaFernández Lucas, JesúsGago, FedericoSánchez-Murcia, Pedro Alejandro-will be generated-orcid-0000-0001-8415-870X-600spaUniversidad de la CostaCC0 1.0 Universalhttp://creativecommons.org/publicdomain/zero/1.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Nucleoside 2’-deoxyribosyltransferasesOxocarbenium ionReaction intermediateReaction mechanism of nucleoside 2’-deoxyribosyltransferases: free-energy landscape supports an oxocarbenium ion as the reaction intermediatePre-Publicaciónhttp://purl.org/coar/resource_type/c_816bTextinfo:eu-repo/semantics/preprinthttp://purl.org/redcol/resource_type/ARTOTRinfo:eu-repo/semantics/acceptedVersionPublicationORIGINALReaction mechanism of nucleoside 2’-deoxyribosyltransferases.pdfReaction mechanism of nucleoside 2’-deoxyribosyltransferases.pdfapplication/pdf115648https://repositorio.cuc.edu.co/bitstreams/509421b9-1ab9-45bb-93d9-6578d78f21ae/download9a12121cfa0c2ba0d7431489944b458dMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8701https://repositorio.cuc.edu.co/bitstreams/76acbfbe-fd34-4422-8cb9-69e16bb6050b/download42fd4ad1e89814f5e4a476b409eb708cMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repositorio.cuc.edu.co/bitstreams/72a2e534-6525-489e-a8c2-5dd7fcf013bd/download8a4605be74aa9ea9d79846c1fba20a33MD53THUMBNAILReaction mechanism of nucleoside 2’-deoxyribosyltransferases.pdf.jpgReaction mechanism of nucleoside 2’-deoxyribosyltransferases.pdf.jpgimage/jpeg2183https://repositorio.cuc.edu.co/bitstreams/5f282022-a5f5-47c0-8a9c-ab63c27a73f2/download730613039be56a20b9ea9e41cccfb32bMD54Reaction mechanism of nucleoside 2’-deoxyribosyltransferases.pdf.jpgReaction mechanism of nucleoside 2’-deoxyribosyltransferases.pdf.jpgimage/jpeg38161https://repositorio.cuc.edu.co/bitstreams/a2076520-4d42-4fb5-a5dc-a3e47968a9a0/download290ef00377d85d316a30d0665b5dd6c6MD55THUMBNAILTEXTReaction mechanism of nucleoside 2’-deoxyribosyltransferases.pdf.txtReaction mechanism of nucleoside 2’-deoxyribosyltransferases.pdf.txttext/plain1081https://repositorio.cuc.edu.co/bitstreams/f13bd0cc-a229-4240-a0b7-223b0dedc5c6/download1c5539e7e710ee39388f083a020fa4d1MD5611323/5253oai:repositorio.cuc.edu.co:11323/52532024-09-17 10:46:59.094http://creativecommons.org/publicdomain/zero/1.0/CC0 1.0 Universalopen.accesshttps://repositorio.cuc.edu.coRepositorio de la Universidad de la Costa CUCrepdigital@cuc.edu.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 |