NMR study of the sites of human hemoglobin acetylated by aspirin

Xu, Arron S.L.; Macdonald, Jeffrey M.; Labotka, Richard; London, Robert E.

doi:10.1016/s0167-4838(99)00094-1

Cited by 22 publications

(30 citation statements)

References 38 publications

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“…All other reagents were of analytical grade. Human hemoglobin A was prepared using the protocol reported in our previous study (12). [1Ј- 13 C]Aspirin was synthesized using the procedures reported elsewhere (12,13).…”

Section: Methodsmentioning

confidence: 99%

“…Human hemoglobin A was prepared using the protocol reported in our previous study (12). [1Ј- 13 C]Aspirin was synthesized using the procedures reported elsewhere (12,13). [1-13 C]Methyl acetylphosphate was prepared by a reported synthesis procedure (14) using [1-13 C]acetyl bromide as the precursor for isotopic labeling.…”

Section: Methodsmentioning

confidence: 99%

“…The HMQC (15) and HSQC (16) experiments were adapted to acquire the spectra of the chemically modified hemoglobin adducts. Details of spectral acquisition, processing, and analysis are reported elsewhere (12).…”

Section: Methodsmentioning

confidence: 99%

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Acetylation of Human Hemoglobin by Methyl Acetylphosphate

Xu¹,

Labotka²,

London³

1999

Journal of Biological Chemistry

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Biophys. Acta 1432, 333-349). Blocking the 2,3-DPG binding site with inositol hexaphosphate (IHP) resulted in a selective reduction in intensity of adduct resonances, presumably corresponding to residues located in the 2,3-DPG binding cleft. The pattern of residue protection appeared to be identical to that observed in our previous study using IHP and labeled aspirin. Pre-acetylation of hemoglobin using unlabeled MAP, followed by acetylation with [1-13 C]aspirin indicated a general protective effect, with the greatest reduction of intensity for resonances corresponding to acetylated residues in the 2,3-DPG binding site. These studies indicated that both MAP and aspirin exhibit similar, although not identical, acetylation profiles and target primarily the ␤Lys-82 residue in the 2,3-DPG binding site, as well as sites such as ␤Lys-59 and ␣Lys-90, which are not located in the ␤-cleft of hemoglobin.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Acetylation of Human Hemoglobin by Methyl Acetylphosphate

Xu¹,

Labotka²,

London³

1999

Journal of Biological Chemistry

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“…The acetyl-3,5-dibromosalicylic acid (dibromo aspirin), a derivative of aspirin, has been reported to exhibit the erythrocyte sickling [15]. Acetylation of hemoglobin by aspirin and other acetylating agents has been used to generate haemoglobin analogs with altered structural and functional properties, and may prove useful in the treatment of sickle cell disease [16].…”

Section: Mode Of Action Of Aspirin and Nsaidsmentioning

confidence: 99%

Structure Activity Relationship (SAR) of Some Benzoic Acid Derivatives from Plant Origin that Exhibit Anti-Sickling Properties in vitro - (Review)

Pierre¹,

Moses²,

Peter³

2015

Nat Prod Chem Res 2015

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“…SNA was chosen previously to probe the surface Lys residue on the plasma transglutaminase, Factor XIIIA 20 and several other enzymes. 21 Another pharmacologic acetylating agent, aspirin (acetyl salicylic; ASA), which is a common anti-inflammatory agent, acetylated Lys residues in several molecules including antithrombin III, 22 hemoglobin, 23,24 fibrinogen 25 and BSA. 26 Since ASA can be administered orally to humans, it could serve as a practical method to modulate the activity of TGM2.…”

Section: Resultsmentioning

confidence: 99%

Human tissue transglutaminase is inhibited by pharmacologic and chemical acetylation

2010

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Human tissue transglutaminase (TGM2) is implicated in the pathogenesis of several neurodegenerative disorders including Alzheimer's, Parkinson's and expanded polyglutamine (polyQ) diseases. TGM2 promotes formation of soluble and insoluble high molecular weight aggregates by catalyzing a covalent linkage between peptide-bound Q residues in polyQ proteins and a peptide-bound Lys residue. Therapeutic approaches to modulate the activity of TGM2 are needed to proceed with studies to test the efficacy of TGM2 inhibition in disease processes. We investigated whether acetylation of Lys-residues by sulfosuccinimidyl acetate (SNA) or aspirin (ASA) would alter the crosslinking activity of TGM2. Acetylation by either SNA and/or ASA resulted in a loss of >90% of crosslinking activity. The Lys residues that were critical for inhibition were identified by mass spectrometry as Lys . Hence, acetylation of Lys-residues may modulate the enzymatic function of TGM2 in vivo and offer a novel approach to treatment of TGM2 mediated disorders.

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NMR study of the sites of human hemoglobin acetylated by aspirin

Cited by 22 publications

References 38 publications

Acetylation of Human Hemoglobin by Methyl Acetylphosphate

Acetylation of Human Hemoglobin by Methyl Acetylphosphate

Structure Activity Relationship (SAR) of Some Benzoic Acid Derivatives from Plant Origin that Exhibit Anti-Sickling Properties in vitro - (Review)

Human tissue transglutaminase is inhibited by pharmacologic and chemical acetylation

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