Effects of Glutathione and Histidine on NO Release from a Dimeric Dinitrosyl Iron Complex (DNIC).

Published on Nov 13, 2020in Inorganic Chemistry4.825
· DOI :10.1021/ACS.INORGCHEM.0C02196
D. Chase Pectol2
Estimated H-index: 2
(A&M: Texas A&M University),
Sarosh Khan9
Estimated H-index: 9
(A&M: Texas A&M University)
+ 3 AuthorsMarcetta Y. Darensbourg65
Estimated H-index: 65
(A&M: Texas A&M University)
Rates of NO release from synthetic dinitrosyl iron complexes (DNICs) are shown to be responsive to coordination environments about iron. The effect of biologically relevant cellular components, glutathione and histidine, on the rate of NO release from a dimeric, "Roussin's Red Ester", DNIC with bridging μ-S thioglucose ligands, SGlucRRE or [(μ-SGluc)Fe(NO)2]2 (SGluc = 1-thio-β-d-glucose tetraacetate), was investigated. From the Griess assay and X-band EPR data, decomposition of the product from the histidine-cleaved dimer, [(SGluc)(NHis)Fe(NO)2], generated Fe(III) and increased the NO release rate in aqueous media when compared to the intact SGlucRRE precursor. In contrast, increasing concentrations of exogenous glutathione generated the stable [(SGluc)(GS)Fe(NO)2]- anion and depressed the rate of NO release. Both of the cleaved, monomeric intermediates were characterized with ESI-MS, EPR, and FT-IR spectroscopies. On the basis of the Griess assay coupled with data from an intracellular fluorometric probe, both the monomeric DNICs and dimeric SGlucRRE diffuse into smooth muscle cells, chosen as appropriate archetypes of vascular relaxation, and release their NO payload. Ultimately, this work provides insight into tuning NO release beyond the design of DNICs, through the incubation with safe, accessible biological molecules.
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#1Luiz Gonzaga de França Lopes (UFC: Federal University of Ceará)H-Index: 17
#2Florêncio Sousa Gouveia Júnior (UFC: Federal University of Ceará)H-Index: 1
Last. Izaura C.N. Diógenes (UFC: Federal University of Ceará)H-Index: 15
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Abstract null null The diatomic molecules, O2, NO and CO, have had a myriad of roles in biology. Due to this, nature has developed many sensing proteins to perceive and respond to changes in the levels of these molecules. The large majority of these proteins are metalloproteins, due to the capacity of metals to bind efficiently to those diatomic molecules. At the same time, nature developed advanced structural and electronic adjustments to fine tune these proteins for sensing, enabling them to f...
#1D. Chase Pectol (A&M: Texas A&M University)H-Index: 2
#2Christopher R DeLaney (A&M: Texas A&M University)
Last. Marcetta Y. Darensbourg (A&M: Texas A&M University)H-Index: 65
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By repurposing DNICs designed for other medicinal purposes, the possibility of protease inhibition was investigated in silico using AutoDock 4.2.6 (AD4) and in vitro via a FRET protease assay. AD4 was validated as a predictive computational tool for coordinatively unsaturated DNIC binding using the only known crystal structure of a protein-bound DNIC, PDB-1ZGN (calculation RMSD = 1.77). From the in silico data the dimeric DNICs TGTA-RRE, [(μ-S-TGTA)Fe(NO)2]2 (TGTA = 1-thio-β-d-glucose tetraaceta...