Identification of a Nickel(II) Binding Site on Hemoglobin Which Confers Susceptibility to Oxidative Deamination and Intramolecular Cross-linking

Levine, Jay F.; Weickert, Michael J.; Pagratis, Maria; Etter, Jeff; Mathews, Antony J.; Fattor, Tim; Lippincott, Julie; Apostoł, Izydor

doi:10.1074/jbc.273.21.13037

Cited by 23 publications

(29 citation statements)

References 40 publications

(35 reference statements)

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“…Additionally, the GGH peptide is known to undergo oxidative degradation, including decarboxylation in the presence of ambient oxygen or other oxidizers (6,14,30). These results, along with our finding of oxidative deamination only on ␣-carbon amines in His-2 peptides, indicate a unique structural specificity for a sequence motif that was first discovered in the ␤-chain of human hemoglobin (15).…”

Section: Quenching and Inhibition Studies Of Deamination Of Lh Dipeptsupporting

confidence: 64%

“…Derivatization with 2,4,-Dinitrophenylhydrazine-Derivatizations were performed as described previously (15). * The costs of publication of this article were defrayed in part by the payment of page charges.…”

Section: Methodsmentioning

confidence: 99%

“…Reaction (15). Therefore, as a comparison with the AHA peptide, we examined the reactivity of the tripeptide AAA.…”

Section: Reaction Of the Ni(ii)-complexed Tripeptide Ala-his-ala Withmentioning

confidence: 99%

“…We have recently reported on the identification of a unique Ni(II) binding site on hemoglobin that, in the presence of monoperoxysulfate, produces N-terminal oxidative deamination, as well as intramolecular cross-linking, both specific to the ␤-globins (15). In the present study, we have employed small model peptides in order to verify the structural assignment of oxidative deamination, as well as to identify the minimal sequence requirements for reaction susceptibility.…”

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confidence: 99%

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Nickel-catalyzed N-terminal Oxidative Deamination in Peptides Containing Histidine at Position 2 Coupled with Sulfite Oxidation

Levine

Etter

Apostoł

1999

Journal of Biological Chemistry

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Peptides containing histidine at position 2 were observed to undergo spontaneous N-terminal oxidative deamination in aqueous solution in the presence of Ni(II), sulfite, and ambient oxygen. The reaction resulted in the formation of a free carbonyl on the Nterminal ␣-carbon (␣-ketoamide) and was catalytic with respect to nickel. This oxidative deamination was confirmed by 13 C NMR, 1 H NMR, mass spectrometry, and chemical tests. No evidence of modification of histidine was found. It was demonstrated that the nickel-dependent N-terminal oxidative deamination also occurred in His-2 peptides using potassium peroxymonosulfate (oxone) as an oxidant. When oxone was used, oxygen was not required for the deamination to proceed. The results suggest that both nickel-catalyzed reactions (sulfite and oxygen, and oxone) produce an imine intermediate that spontaneously hydrolyzes to form the free carbonyl. These findings may provide a physiologically relevant model for oxidative carbonyl formation in vivo, as well as a useful method for producing a site-specific carbonyl on peptides and proteins.Excessive exposures to both nickel and sulfite are known to produce serious toxic and carcinogenic effects in animals and humans (1-4). The generation of potentially harmful radicals from sulfite oxidation by transition metal catalysis has been well established (5). Nickel salts are physiologically redoxinactive, and therefore nickel toxicity in vivo is inferred to involve activation by coordination with peptides and proteins. A variety of catalytic oxidative properties of Ni(II)/peptide complexes have been reported in the literature. These include decarboxylation of the Ni(II)-Gly-Gly-His complex in the presence of molecular oxygen (6), the ability of Ni(II)-histidyl peptide complexes to function as Fenton reaction catalysts (7,8), and the ability of the Ni(II)-Gly-Gly-L-His complex to catalyze the oxidation and cleavage of DNA (9, 10) and to promote the formation of intermolecular protein cross-links (11, 12). Muller et al. (13) and Liang et al. (14) have recently reported that autooxidation of sulfite catalyzed by the Ni(II)-complexed LysGly-His-amide tripeptide can oxidatively damage DNA. They postulate in situ formation of monoperoxysulfate, a strong oxidant, as an active intermediate in the damaging effect.We have recently reported on the identification of a unique Ni(II) binding site on hemoglobin that, in the presence of monoperoxysulfate, produces N-terminal oxidative deamination, as well as intramolecular cross-linking, both specific to the ␤-globins (15). In the present study, we have employed small model peptides in order to verify the structural assignment of oxidative deamination, as well as to identify the minimal sequence requirements for reaction susceptibility. Additionally, we have tested a system that substitutes sulfite (SO 3 2Ϫ ) and oxygen (O 2 ) for potassium peroxymonosulfate (oxone). 1 Our findings show clearly that histidine at position 2 is a fundamental requirement for Ni(II)-catalyzed oxidative Ntermina...

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Section: Quenching and Inhibition Studies Of Deamination Of Lh Dipeptsupporting

confidence: 64%

Section: Methodsmentioning

confidence: 99%

“…Reaction (15). Therefore, as a comparison with the AHA peptide, we examined the reactivity of the tripeptide AAA.…”

Section: Reaction Of the Ni(ii)-complexed Tripeptide Ala-his-ala Withmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Nickel-catalyzed N-terminal Oxidative Deamination in Peptides Containing Histidine at Position 2 Coupled with Sulfite Oxidation

Levine

Etter

Apostoł

1999

Journal of Biological Chemistry

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“…Because Pb binds exclusively to hemoglobin molecule in erythrocytes [59], a VLBW infant who might have been transfused with pRBC would receive nearly double the concentration of heavy metals initially present in the donor blood [15]. Several studies suggest that other metals also bind to hemoglobin [60][61][62][63][64][65]. The difference in metal concentrations between whole blood versus pRBCs may not be a trivial issue.…”

Section: Discussionmentioning

confidence: 99%

Toxic Metal Contamination of Banked Blood Designated for Neonatal Transfusion

Sundararajan¹,

Blatz²,

Dearborn³

et al. 2015

J Clin Toxicol

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Objective: Very low birth weight (VLBW) infants frequently receive blood transfusions. We hypothesize that toxic metals in donor blood may pose a health risk with potential adverse neurologic effects on the developing brain of a vulnerable VLBW infant. Study design:Samples from 100 donor blood units were collected from a large urban hospital. Blood was analyzed for aluminum, arsenic, beryllium, cadmium, manganese, mercury, nickel, lead and polonium. The estimated upper limit of acceptable metal concentration in donor blood was calculated assuming a transfusion volume of 20 ml/kg and using either previously published acceptable intravenous doses or oral reference doses with a conservative estimate of 10% gastrointestinal absorption. Ingested mercury was assumed to be 95% absorbed.Results: Eight of the nine metals were detectable. Concentrations of arsenic, beryllium, cadmium, mercury and polonium were not of concern for any single blood transfusion. Concentrations of aluminum, manganese, nickel and lead exceeded the estimated upper limit of acceptable concentration in 5, 11, 4 and 26 units respectively. Of the 100 units, 31 had at least one toxic metal concentration high enough to pose a potential health risk.Conclusions: VLBW infants are exposed to heavy metals that are toxic from blood transfusion. The number of units with concerning levels of toxic metals was higher than expected. Neonatologists should be aware of this potential exposure to toxic metals from donor blood when decision is made to administer blood transfusion. Neurodevelopmental studies of toxic metal exposed infants from blood transfusion are warranted.

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Hemoglobin depletion from plasma: Considerations for proteomic discovery in Sickle Cell disease and other hemolytic processes

Williams

Dulloor

et al. 2010

Proteomics Clinical Apps

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Purpose Hemoglobin (Hb) depletion with nickel affinity chromatography has been shown to increase the number of proteins identified in proteomic studies of erythrocytes, but limited data exist on the application of this technique in depletion of Hb from plasma or serum required for clinical biomarker studies. The aim of this study was to explore the potential of using nickel-beads for Hb depletion of plasma. Experimental design Nickel-nitrilotriacetic acid (Ni-NTA) affinity chromatography was used to deplete Hb from hemolyzed plasma samples obtained from children with sickle cell disease (SCD, n=7) and normal human plasma (n=4). Ni-NTA bound proteins were analyzed by one-dimensional gel electrophoresis, followed by in-gel digestion for characterization using a LTQ-Orbitrap hybrid mass spectrometer. In addition, the loss of two non-hemoglobin related plasma proteins, thrombospondin1 (TSP1) and L-selectin, by Ni-NTA was determined by ELISA (SCD n=6, non-SCD controls n=2). Results Ni-NTA resulted in an average 60% decrease in plasma protein concentration, which was not hemolysis dependent. Specifically, Hb (7 peptides) and the top three proteins, alpha-2-macroglobulin (75 peptides), apolipoprotein B-100 (73 peptides), and albumin (42 peptides) were Ni-NTA bound. In addition, using an ELISA assay two non-hemoglobin associated plasma proteins TSP1 and L-selectin were decreased by Ni-NTA. Conclusions and clinical relevance Hb depletion with Ni-NTA is effective for Hb removal but is not specific. There is potential for deleterious depletion of potential biomarkers that may limit the applicability of this method. Consideration of alternate methods of Hb depletion for clinical proteomics may be warranted.

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Identification of a Nickel(II) Binding Site on Hemoglobin Which Confers Susceptibility to Oxidative Deamination and Intramolecular Cross-linking

Cited by 23 publications

References 40 publications

Nickel-catalyzed N-terminal Oxidative Deamination in Peptides Containing Histidine at Position 2 Coupled with Sulfite Oxidation

Nickel-catalyzed N-terminal Oxidative Deamination in Peptides Containing Histidine at Position 2 Coupled with Sulfite Oxidation

Toxic Metal Contamination of Banked Blood Designated for Neonatal Transfusion

Hemoglobin depletion from plasma: Considerations for proteomic discovery in Sickle Cell disease and other hemolytic processes

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