Histidine and Proline are Important Sites of Free Radical Damage to Proteins

Dean, Roger T.; Wolff, Simon P.; McElligott, Mary Ann

doi:10.3109/10715768909087929

Cited by 92 publications

(51 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3B). The addition of His, which chelates Cu(II)/Cu(I) (43,44), blocked protein fragmentation and protein radicals (Fig. 4), whereas the addition of methionine to the reaction mixture does not affect protein radical formation, suggesting that, under our experimental conditions, this amino acid is involved in neither copper binding nor DMPO nitrone adduct formation.…”

Section: Discussionmentioning

confidence: 78%

Copper-catalyzed Protein Oxidation and Its Modulation by Carbon Dioxide

Ramirez

Gomez-Mejiba

Mason

2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

It is well known that hydrogen peroxide (H 2 O 2 )-induced copper-catalyzed fragmentation of proteins follows a site-specific oxidative mechanism mediated by hydroxyl radical-like species (i.e. Cu(I)O, Cu(II)/ ⅐ OH or Cu(III)) that ends in increased carbonyl formation and protein fragmentation. We have found that the nitrone spin trap DMPO (5,5-dimethyl-1-pyrroline N-oxide) prevented such processes by trapping human serum albumin (HSA)-centered radicals, in situ and in real time, before they reacted with oxygen. When (bi)carbonate (CO 2 , H 2 CO 3 , HCO 3 ؊ , and CO 3 ؊2 ) was added to the reaction mixture, it blocked fragmentation mediated by hydroxyl radical-like species but enhanced DMPO-trappable radical sites in HSA. In the past, this effect would have been explained by oxidation of (bi)carbonate to a carbonate radical anion (CO 3 . ) by a bound hydroxyl rad-

show abstract

Section: Discussionmentioning

confidence: 78%

Copper-catalyzed Protein Oxidation and Its Modulation by Carbon Dioxide

Ramirez

Gomez-Mejiba

Mason

2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…These results suggest that copper alloy surfaces have an impact on the HuNoV capsid in a region associated with receptor binding. Histidine and proline amino acid residues were previously identified as important sites of protein attack mediated by copper radical formation (23). Interestingly, several sites in the P2 domain of the capsid are rich in histidine and/or proline residues.…”

Section: Discussionmentioning

confidence: 99%

Destruction of the Capsid and Genome of GII.4 Human Norovirus Occurs during Exposure to Metal Alloys Containing Copper

Manuel

Moore

Jaykus

2015

Appl Environ Microbiol

View full text Add to dashboard Cite

Human norovirus (HuNoV) represents a significant public health burden worldwide and can be environmentally transmitted. Copper surfaces have been shown to inactivate the cultivable surrogate murine norovirus, but no such data exist for HuNoV. The purpose of this study was to characterize the destruction of GII.4 HuNoV and virus-like particles (VLPs) during exposure to copper alloy surfaces. Fecal suspensions positive for a GII.4 HuNoV outbreak strain or GII.4 VLPs were exposed to copper alloys or stainless steel for 0 to 240 min and recovered by elution. HuNoV genome integrity was assessed by reverse transcriptionquantitative PCR (RT-qPCR) (without RNase treatment), and capsid integrity was assessed by RT-qPCR (with RNase treatment), transmission electron microscopy (TEM), SDS-PAGE/Western blot analysis, and a histo-blood group antigen (HBGA) binding assay. Exposure of fecal suspensions to pure copper for 60 min reduced the GII.4 HuNoV RNA copy number by ϳ3 log 10 units when analyzed by RT-qPCR without RNase treatment and by 4 log 10 units when a prior RNase treatment was used. The rate of reduction of the HuNoV RNA copy number was approximately proportional to the percentage of copper in each alloy. Exposure of GII.4 HuNoV VLPs to pure-copper surfaces resulted in noticeable aggregation and destruction within 240 min, an 80% reduction in the VP1 major capsid protein band intensity in 15 min, and a near-complete loss of HBGA receptor binding within 8 min.In all experiments, HuNoV remained stable on stainless steel. These results suggest that copper surfaces destroy HuNoV and may be useful in preventing environmental transmission of the virus in at-risk settings.H uman norovirus (HuNoV) is the leading cause of viral gastroenteritis worldwide (1, 2). In the United States alone, the virus is responsible for 19 million to 21 million illnesses annually, contributing to nearly $500 million in hospital-associated costs each year (3, 4). The illness is characterized by nausea, vomiting, and diarrhea and typically lasts 24 to 48 h. While the disease is usually self-limiting, in individuals belonging to sensitive populations, symptoms can become life threatening if rehydration therapy is ignored.HuNoV transmission occurs via the fecal-oral route, usually through ingestion of contaminated food or water, or by direct contact with an infected individual. Environmental transmission also occurs, and episodes of vomiting or diarrhea can contaminate surfaces with infectious virus particles that may persist for weeks (5). Environmental persistence of HuNoV is enhanced by its resistance to a variety of commonly used sanitizers and disinfectants, for example, alcohol-based hand sanitizers and hypochlorite at regulated concentrations (6, 7). These unique traits of HuNoV, combined with the low infectious dose and the fact that infected individuals shed a large amount of virus in both fecal material and vomitus, contribute to the high number of outbreaks observed annually in environments with close quarters such as cruise ships, restau...

show abstract

“…Indeed proline (and histidine) is an important site of HOd attack on BSA, although the predicted product(s) from cleavage at this site could not be detected, while new products arising from proline were formed [118]. This putative pathway has been observed in simple peptide systems [119], but is inconsistent with the reported stability of the α-carbon radical formed from proline (see [120]).…”

Section: Features Of Radical-mediated Protein Fragmentation and Polymmentioning

confidence: 94%

Biochemistry and pathology of radical-mediated protein oxidation

Dean

Stocker

et al. 1997

Biochemical Journal

Self Cite

1,545

982

View full text Add to dashboard Cite

Radical-mediated damage to proteins may be initiated by electron leakage, metal-ion-dependent reactions and autoxidation of lipids and sugars. The consequent protein oxidation is O2-dependent, and involves several propagating radicals, notably alkoxyl radicals. Its products include several categories of reactive species, and a range of stable products whose chemistry is currently being elucidated. Among the reactive products, protein hydroperoxides can generate further radical fluxes on reaction with transition-metal ions; protein-bound reductants (notably dopa) can reduce transition-metal ions and thereby facilitate their reaction with hydroperoxides; and aldehydes may participate in Schiff-base formation and other reactions. Cells can detoxify some of the reactive species, e.g. by reducing protein hydroperoxides to unreactive hydroxides. Oxidized proteins are often functionally inactive and their unfolding is associated with enhanced susceptibility to proteinases. Thus cells can generally remove oxidized proteins by proteolysis. However, certain oxidized proteins are poorly handled by cells, and together with possible alterations in the rate of production of oxidized proteins, this may contribute to the observed accumulation and damaging actions of oxidized proteins during aging and in pathologies such as diabetes, atherosclerosis and neurodegenerative diseases. Protein oxidation may also sometimes play controlling roles in cellular remodelling and cell growth. Proteins are also key targets in defensive cytolysis and in inflammatory self-damage. The possibility of selective protection against protein oxidation (antioxidation) is raised.

show abstract

Histidine and Proline are Important Sites of Free Radical Damage to Proteins

Cited by 92 publications

References 22 publications

Copper-catalyzed Protein Oxidation and Its Modulation by Carbon Dioxide

Copper-catalyzed Protein Oxidation and Its Modulation by Carbon Dioxide

Destruction of the Capsid and Genome of GII.4 Human Norovirus Occurs during Exposure to Metal Alloys Containing Copper

Biochemistry and pathology of radical-mediated protein oxidation

Contact Info

Product

Resources

About