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[PMID]: | 25146761 |
[Au] Autor: | Pietra F |
[Ad] Endereço: | Accademia Lucchese di Scienze, Lettere e Arti, Classe di Scienze, Palazzo Ducale, Lucca I-55100, (phone/fax: +39-0583-417336). francesco.pietra@accademialucchese.it. |
[Ti] Título: | Binding pockets and pathways for dioxygen through the KijD3 N-oxygenase in complex with flavin mononucleotide cofactor and a 3-aminoglucose substrate: predictions from molecular dynamics simulations. |
[So] Source: | Chem Biodivers;11(8):1151-62, 2014 Aug. | [Is] ISSN: | 1612-1880 |
[Cp] País de publicação: | Switzerland |
[La] Idioma: | eng |
[Ab] Resumo: | In this work, two protein systems, Kij3D-FMN-AKM-O2 and Kij3D-FMN-O2 , made of KijD3 N-oxygenase, flavin mononucleotide (FMN) cofactor, dTDP-3-amino-2,3,6-trideoxy-4-keto-3-methyl-D-glucose (AKM) substrate, and dioxygen (O2), have been assembled by adding a molecule of O2, and removing (or not) AKM, to crystal data for the Kij3D-FMN-AKM complex. Egress of AKM and O2 from these systems was then investigated by applying a tiny external random force, in turn, to their center of mass in the course of molecular dynamics in explicit H2 O. It turned out that the wide AKM channel, even when emptied, does not constitute the main route for O2 egress. Other routes appear to be also viable, while various binding pockets (BPs) outside the active center are prone to trap O2. By reversing the reasoning, these can also be considered as routes for uptake of O2 by the protein, before or after AKM uptake, while BPs may serve as reservoirs of O2. This shows that the small molecule O2 is capable of permeating the protein by exploiting all nearby interstices that are created on thermal fluctuations of the protein, rather than having necessarily to look for farther, permanent channels. |
[Mh] Termos MeSH primário: |
Mononucleotídeo de Flavina/química Oxigênio/metabolismo Oxigenases/química Oxigenases/metabolismo
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[Mh] Termos MeSH secundário: |
Sítios de Ligação Mononucleotídeo de Flavina/metabolismo Modelos Moleculares Simulação de Dinâmica Molecular Nocardiaceae/enzimologia Conformação Proteica
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 7N464URE7E (Flavin Mononucleotide); EC 1.13.- (Oxygenases); S88TT14065 (Oxygen) |
[Em] Mês de entrada: | 1505 |
[Cu] Atualização por classe: | 140822 |
[Lr] Data última revisão:
| 140822 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 140823 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1002/cbdv.201400081 |
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