Journal article
Oxygen Pathways and Allostery in Monomeric Sarcosine Oxidase via Single-Sweep Free-Energy Reconstruction
Journal of chemical theory and computation, v 10(7), pp 2668-2676
08 Jul 2014
PMID: 25061440
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Monomeric sarcosine oxidase (MSOX) is a flavoprotein D-amino acid oxidase with reported sarcosine and oxygen activation sites on the
and
faces of the flavin ring, respectively. O
transport routes to the catalytic interior are not well understood and are difficult to ascertain solely from MSOX crystal structures. A composite free-energy method known as single-sweep is used to map and thermodynamically characterize oxygen sites and routes leading to the catalytically active Lys265 from the protein surface. The result is a network of pathways and free energies within MSOX illustrating that oxygen can access two free-energy minima on the
face of the reduced flavin from four separate solvent portals. No such minimum is observed on the
face. The pathways are geometrically similar for three major states of the enzyme: (1) apo with a closed flavin cleft, (2) apo with an open flavin cleft, and (3) inhibitor-bound with a closed flavin cleft. Interestingly, free energies along these transport pathways display significantly deeper minima when the substrate-mimicking inhibitor 2-furoic acid is bound at the sarcosine site, even at locations far from this site. This suggests a substrate-dependent allosteric modulation of the kinetics of O
transport from the solvent to the active site.
Metrics
Details
- Title
- Oxygen Pathways and Allostery in Monomeric Sarcosine Oxidase via Single-Sweep Free-Energy Reconstruction
- Creators
- Anthony Bucci - Dept. Chemical and Biological Engineering, Drexel University , Philadelphia, Pennsylvania 19104, United StatesCameron F Abrams - Dept. Chemical and Biological Engineering, Drexel University , Philadelphia, Pennsylvania 19104, United States
- Publication Details
- Journal of chemical theory and computation, v 10(7), pp 2668-2676
- Publisher
- American Chemical Society; Washington, DC
- Grant note
- R01 GM100472 / NIGMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Web of Science ID
- WOS:000338805900005
- Scopus ID
- 2-s2.0-84904134726
- Other Identifier
- 991014878327604721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Chemistry, Physical
- Physics, Atomic, Molecular & Chemical