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January 1, 2001Journal of Biological ChemistryOpen Access

Neuronal Nitric-oxide Synthase Mutant (Ser-1412 → Asp) Demonstrates Surprising Connections between Heme Reduction, NO Complex Formation, and Catalysis

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Key result

The S1412D mutation in nNOS speeds electron transfer and intrinsic NO synthesis but diminishes NO release in the steady state, revealing the importance of heme reduction rate.

Population

Rat neuronal NO synthase (nNOS)

Comparison

Ser-1412 to Asp mutation in the reductase domain vs Wild-type nNOS

Design

Preclinical

Authors

SASubrata AdakJSJérôme SantoliniSTSvetlana B. Tikunova

Discussion

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Overview

No immediate clinical relevance; extends mechanistic understanding of nNOS heme reduction in animal models.

Structured PICO

P
Population
Rat neuronal NO synthase (nNOS)
I
Intervention
Ser-1412 to Asp (S1412D) mutation in the reductase domain
C
Comparator
Wild-type nNOS
O
Outcome
Catalytic parameters including cytochrome c and ferricyanide reduction, steady-state NO synthesis, and heme reduction ratessurrogate

The S1412D mutation in nNOS demonstrates that the rate of heme reduction is critical in controlling steady-state NO synthesis and release.

Cite This Study

Adak et al. (2001) studied this question. S1412D mutation in rat neuronal NO synthase (nNOS) vs. Wild-type nNOS was evaluated on Catalytic parameters including heme reduction, NO complex formation, and steady-state NO synthesis. The S1412D mutation in nNOS speeds electron transfer and intrinsic NO synthesis but diminishes NO release in the steady state, revealing the importance of heme reduction rate.

synapsesocial.com/papers/6a93a2ed0799a276a31f5a2chttps://doi.org/10.1074/jbc.m006857200
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Molecular Basis for Hyperactivity in Tryptophan 409 Mutants of Neuronal NO Synthase2000 · 52 citations
  2. 2The Crucial Roles of Asp-314 and Thr-315 in the Catalytic Activation of Molecular Oxygen by Neuronal Nitric-oxide Synthase1998 · 31 citations
  3. 3Electron Transfer and Catalytic Activity of Nitric Oxide Synthases1998 · 99 citations
  4. 4A Kinetic Simulation Model That Describes Catalysis and Regulation in Nitric-oxide Synthase2001 · 97 citations
  5. 5Regulation of Neuronal Nitric-oxide Synthase by Calmodulin Kinases1999 · 180 citations