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Bacterial denitrifying nitric oxide reductases and aerobic respiratory terminal oxidases use similar delivery pathways for their molecular substrates.

Authors
  • Mahinthichaichan, Paween1
  • Gennis, Robert B2
  • Tajkhorshid, Emad3
  • 1 Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Street, Urbana, IL 61801, USA; NIH Center for Macromolecular Modeling and Bioinformatics, 405 North Mathews Avenue, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, 405 N. Mathews Avenue, Urbana, IL 61801, USA.
  • 2 Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Street, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, 179 Looomis, MC-704, 1110 Green Street, Urbana, IL 61801, USA. Electronic address: [email protected]
  • 3 Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Street, Urbana, IL 61801, USA; NIH Center for Macromolecular Modeling and Bioinformatics, 405 North Mathews Avenue, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, 405 N. Mathews Avenue, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, 179 Looomis, MC-704, 1110 Green Street, Urbana, IL 61801, USA. Electronic address: [email protected]
Type
Published Article
Journal
Biochimica et Biophysica Acta (BBA) - Bioenergetics
Publisher
Elsevier
Publication Date
Sep 01, 2018
Volume
1859
Issue
9
Pages
712–724
Identifiers
DOI: 10.1016/j.bbabio.2018.06.002
PMID: 29883591
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The superfamily of heme‑copper oxidoreductases (HCOs) include both NO and O2 reductases. Nitric oxide reductases (NORs) are bacterial membrane enzymes that catalyze an intermediate step of denitrification by reducing nitric oxide (NO) to nitrous oxide (N2O). They are structurally similar to heme‑copper oxygen reductases (HCOs), which reduce O2 to water. The experimentally observed apparent bimolecular rate constant of NO delivery to the deeply buried catalytic site of NORs was previously reported to approach the diffusion-controlled limit (108-109 M-1 s-1). Using the crystal structure of cytochrome-c dependent NOR (cNOR) from Pseudomonas aeruginosa, we employed several protocols of molecular dynamics (MD) simulation, which include flooding simulations of NO molecules, implicit ligand sampling and umbrella sampling simulations, to elucidate how NO in solution accesses the catalytic site of this cNOR. The results show that NO partitions into the membrane, enters the enzyme from the lipid bilayer and diffuses to the catalytic site via a hydrophobic tunnel that is resolved in the crystal structures. This is similar to what has been found for O2 diffusion through the closely related O2 reductases. The apparent second order rate constant approximated using the simulation data is ~5 × 108 M-1 s-1, which is optimized by the dynamics of the amino acid side chains lining in the tunnel. It is concluded that both NO and O2 reductases utilize well defined hydrophobic tunnels to assure that substrate diffusion to the buried catalytic sites is not rate limiting under physiological conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

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