What does this research mean for the field?

The C-terminus of endothelial nitric-oxide synthase (eNOS) functions as an autoinhibitory domain that restricts calmodulin-dependent activation, a barrier that is functionally disabled by phosphorylation at Ser1179 to enable calcium-independent NO synthesis. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To determine whether Ser1179 phosphorylation activates endothelial nitric oxide synthase (eNOS) by relieving an intrinsic C-terminal autoinhibitory barrier.

May 1, 2002Journal of Biological ChemistryOpen Access

Disabling a C-terminal Autoinhibitory Control Element in Endothelial Nitric-oxide Synthase by Phosphorylation Provides a Molecular Explanation for Activation of Vascular NO Synthesis by Diverse Physiological Stimuli

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Population

Bovine endothelial nitric-oxide synthase (eNOS) model

Comparison

Mutant eNOS lacking C-terminal residues 1179-1205 vs Wild type bovine eNOS

Design

Preclinical

Authors

PLPaul LaneCharing Cross Hospital SGSteven S. GrossCornell University

Discussion

Member takes

Implication

No immediate clinical implications for vascular therapies; extends eNOS regulation insights in animal models.

Key Points

To determine whether Ser1179 phosphorylation activates endothelial nitric oxide synthase (eNOS) by relieving an intrinsic C-terminal autoinhibitory barrier.
Used structural protein modeling to evaluate potential autoinhibitory roles of the eNOS C terminus.
Compared enzymatic phenotypes and calmodulin-binding properties of wild-type bovine eNOS against a mutant lacking C-terminal residues 1179–1205 (CDelta27 eNOS).
The CDelta27 mutant exhibited unaltered calmodulin affinity compared to wild-type eNOS.
The CDelta27 mutant demonstrated a 5-fold reduction in the EC50 for calcium and a 2- to 4-fold increase in maximal catalytic activities, functionally mimicking phospho-Ser1179 wild-type eNOS.

Structured PICO

Population

Bovine endothelial nitric-oxide synthase (eNOS) model

Intervention

Mutant eNOS lacking C-terminal residues 1179-1205 (CDelta27 eNOS)

Comparator

Wild type bovine eNOS

Outcome

Enzyme activation properties (EC50 for calcium, maximal catalytic activities, calmodulin affinity)surrogate

The C-terminus of eNOS acts as an autoinhibitory element that is functionally disabled by Ser(1179) phosphorylation, providing a molecular basis for calcium-independent activation of vascular NO synthesis.

Cite This Study

Lane et al. (2002) studied this question.

synapsesocial.com/papers/6a1ea83e989adebfe89a6ab4 https://doi.org/10.1074/jbc.m200258200

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Disabling a C-terminal Autoinhibitory Control Element in Endothelial Nitric-oxide Synthase by Phosphorylation Provides a Molecular Explanation for Activation of Vascular NO Synthesis by Diverse Physiological Stimuli

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Disabling a C-terminal Autoinhibitory Control Element in Endothelial Nitric-oxide Synthase by Phosphorylation Provides a Molecular Explanation for Activation of Vascular NO Synthesis by Diverse Physiological Stimuli

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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