Cargando…
Elucidating nitric oxide synthase domain interactions by molecular dynamics
Nitric oxide synthase (NOS) is a multidomain enzyme that catalyzes the production of nitric oxide (NO) by oxidizing l‐Arg to NO and L‐citrulline. NO production requires multiple interdomain electron transfer steps between the flavin mononucleotide (FMN) and heme domain. Specifically, NADPH‐derived e...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815339/ https://www.ncbi.nlm.nih.gov/pubmed/26448477 http://dx.doi.org/10.1002/pro.2824 |
_version_ | 1782424576315097088 |
---|---|
author | Hollingsworth, Scott A. Holden, Jeffrey K. Li, Huiying Poulos, Thomas L. |
author_facet | Hollingsworth, Scott A. Holden, Jeffrey K. Li, Huiying Poulos, Thomas L. |
author_sort | Hollingsworth, Scott A. |
collection | PubMed |
description | Nitric oxide synthase (NOS) is a multidomain enzyme that catalyzes the production of nitric oxide (NO) by oxidizing l‐Arg to NO and L‐citrulline. NO production requires multiple interdomain electron transfer steps between the flavin mononucleotide (FMN) and heme domain. Specifically, NADPH‐derived electrons are transferred to the heme‐containing oxygenase domain via the flavin adenine dinucleotide (FAD) and FMN containing reductase domains. While crystal structures are available for both the reductase and oxygenase domains of NOS, to date there is no atomic level structural information on domain interactions required for the final FMN‐to‐heme electron transfer step. Here, we evaluate a model of this final electron transfer step for the heme–FMN–calmodulin NOS complex based on the recent biophysical studies using a 105‐ns molecular dynamics trajectory. The resulting equilibrated complex structure is very stable and provides a detailed prediction of interdomain contacts required for stabilizing the NOS output state. The resulting equilibrated complex model agrees well with previous experimental work and provides a detailed working model of the final NOS electron transfer step required for NO biosynthesis. |
format | Online Article Text |
id | pubmed-4815339 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48153392016-04-15 Elucidating nitric oxide synthase domain interactions by molecular dynamics Hollingsworth, Scott A. Holden, Jeffrey K. Li, Huiying Poulos, Thomas L. Protein Sci Articles Nitric oxide synthase (NOS) is a multidomain enzyme that catalyzes the production of nitric oxide (NO) by oxidizing l‐Arg to NO and L‐citrulline. NO production requires multiple interdomain electron transfer steps between the flavin mononucleotide (FMN) and heme domain. Specifically, NADPH‐derived electrons are transferred to the heme‐containing oxygenase domain via the flavin adenine dinucleotide (FAD) and FMN containing reductase domains. While crystal structures are available for both the reductase and oxygenase domains of NOS, to date there is no atomic level structural information on domain interactions required for the final FMN‐to‐heme electron transfer step. Here, we evaluate a model of this final electron transfer step for the heme–FMN–calmodulin NOS complex based on the recent biophysical studies using a 105‐ns molecular dynamics trajectory. The resulting equilibrated complex structure is very stable and provides a detailed prediction of interdomain contacts required for stabilizing the NOS output state. The resulting equilibrated complex model agrees well with previous experimental work and provides a detailed working model of the final NOS electron transfer step required for NO biosynthesis. John Wiley and Sons Inc. 2015-10-22 2016-02 /pmc/articles/PMC4815339/ /pubmed/26448477 http://dx.doi.org/10.1002/pro.2824 Text en © 2015 The Protein Society Open access. |
spellingShingle | Articles Hollingsworth, Scott A. Holden, Jeffrey K. Li, Huiying Poulos, Thomas L. Elucidating nitric oxide synthase domain interactions by molecular dynamics |
title | Elucidating nitric oxide synthase domain interactions by molecular dynamics |
title_full | Elucidating nitric oxide synthase domain interactions by molecular dynamics |
title_fullStr | Elucidating nitric oxide synthase domain interactions by molecular dynamics |
title_full_unstemmed | Elucidating nitric oxide synthase domain interactions by molecular dynamics |
title_short | Elucidating nitric oxide synthase domain interactions by molecular dynamics |
title_sort | elucidating nitric oxide synthase domain interactions by molecular dynamics |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815339/ https://www.ncbi.nlm.nih.gov/pubmed/26448477 http://dx.doi.org/10.1002/pro.2824 |
work_keys_str_mv | AT hollingsworthscotta elucidatingnitricoxidesynthasedomaininteractionsbymoleculardynamics AT holdenjeffreyk elucidatingnitricoxidesynthasedomaininteractionsbymoleculardynamics AT lihuiying elucidatingnitricoxidesynthasedomaininteractionsbymoleculardynamics AT poulosthomasl elucidatingnitricoxidesynthasedomaininteractionsbymoleculardynamics |