Cooperative Effect of Multiple Domains in Copper Proteins Applied to H2S Sensing

TL;DR

This paper explores how copper proteins can be used to detect hydrogen sulfide (H2S), a molecule with both toxic and beneficial roles in the body.

Contribution

The study introduces multicopper proteins as versatile and sensitive H2S sensors with advantages over existing methods.

Findings

SLAC, a two-domain copper oxidase, functions as a multiwavelength fluorescent sensor for H2S.

Multicopper proteins outperform Cu-azurin in H2S sensing sensitivity, selectivity, and reversibility.

H2S recognition occurs via selective reduction of copper centers in these proteins.

Abstract

The revolutionary discovery by Abe & Kimura that
H2S exerts a beneficial role in human body has renewed
interest in
this small molecule, long known for its toxicity. Understanding the
(bio)­reactivity of H2S with biological and bioinorganic
targets is therefore of increasing importance, yet studies on its
interaction with nonheme metalloproteins remain limited. Here, we
investigate the reactivity of HS– with two natural
multicopper proteins, SLAC and NiR. We demonstrate that SLAC, a two-domain
blue-copper oxidase, can function as a multiwavelength, multireadout
fluorescent sensor for H2S in complex environments. Comparative
studies on NiR support the proposed mechanism of H2S recognition
via selective reduction of copper centers. Finally, we benchmark the
performance of these multicopper proteins against Cu-azurin, previously
reported as a H2S recognition element, highlighting the
advantages of multicopper architectures in terms of sensitivity, selectivity,
and reversibility. Our findings establish multicopper proteins as
versatile platforms for H2S sensing with potential applications
in biomedical and environmental monitoring.

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