The low p<i>K</i><sub>a</sub> value of iron‐binding ligand Tyr188 and its implication in iron release and anion binding of human transferrin

Sun, Xia; Sun, Hongzhe; Ge, Ruiguang; Richter, Megan; Woodworth, Robert C.; Mason, Anne B.; He, Qing‐Yu

doi:10.1016/j.febslet.2004.07.076

Cited by 17 publications

(13 citation statements)

References 20 publications

(47 reference statements)

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“…It has been proposed that the decrease in cysteine pKa is due to through-space, charge-charge interactions [31]. Lowered pKa values for tyrosine in human transferrin [32] and UDP-galactose 4-epimerase [33] also have been reported. The decrease in pKa was ascribed to interaction with nearby positively charged residues.…”

Section: Discussionmentioning

confidence: 99%

Covalent binding of the organophosphorus agent FP-biotin to tyrosine in eight proteins that have no active site serine

Grigoryan

Anderson

et al. 2009

Chemico-Biological Interactions

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Organophosphorus esters (OP) are known to bind covalently to the active site serine of enzymes in the serine hydrolase family. It was a surprise to find that proteins with no active site serine are also covalently modified by OP. The binding site in albumin, transferrin, and tubulin was identified as tyrosine. The goal of the present work was to determine whether binding to tyrosine is a general phenomenon. Fourteen proteins were treated with a biotin-tagged organophosphorus agent called FP-biotin. The proteins were digested with trypsin and the labeled peptides enriched by binding to monomeric avidin. Peptides were purified by HPLC and fragmented by collision induced dissociation in a tandem ion trap mass spectrometer. Eight proteins were labeled and six were not. Tyrosine was labeled in human alpha-2-glycoprotein 1 zinc-binding protein (Tyr 138, Tyr 174, Tyr 181), human kinesin 3C motor domain (Tyr 145), human keratin 1 (Tyr 230), bovine actin (Tyr 55, Tyr 200), murine ATP synthase beta (Tyr 431), murine adenine nucleotide translocase 1 (Tyr 81), bovine chymotrypsinogen (Tyr 201) and porcine pepsin (Tyr 310). Only 1-3 tyrosines per protein were modified, suggesting that the reactive tyrosine was activated by nearby residues that facilitated ionization of the hydroxyl group of tyrosine. These results suggest that OP binding to tyrosine is a general phenomenon. It is concluded that organophosphorus-reactive proteins include not only enzymes in the serine hydrolase family, but also proteins that have no active site serine. The recognition of a new OP-binding motif to tyrosine suggests new directions to search for mechanisms of long-term effects of OP exposure. Another application is in the search for biomarkers of organophosphorus agent exposure. Previous searches have been limited to serine hydrolases. Now proteins such as albumin and keratin can be considered.

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Section: Discussionmentioning

confidence: 99%

Covalent binding of the organophosphorus agent FP-biotin to tyrosine in eight proteins that have no active site serine

Grigoryan

Anderson

et al. 2009

Chemico-Biological Interactions

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“…1 H‐decoupled 13 C nuclear magnetic resonance (NMR) spectra were recorded on a Bruker DRX500 spectrometer equipped with a 5 mm broad‐band probe as described previously [11,12]. 13 C NMR experiments were performed under 298 K, using 1 mM MtsA protein in 0.1 M KCl solution (10% D 2 O and 90% H 2 O) containing 40 mM NaH 13 CO 3 .…”

Section: Methodsmentioning

confidence: 99%

“…1 H-decoupled 13 C nuclear magnetic resonance (NMR) spectra were recorded on a Bruker DRX500 spectrometer equipped with a 5 mm broad-band probe as described previously [11,12]. 13…”

Section: C Nmrmentioning

confidence: 99%

Lipoprotein MtsA of MtsABC in Streptococcus pyogenes primarily binds ferrous ion with bicarbonate as a synergistic anion

Sun¹,

Ge²,

Chiu³

et al. 2008

FEBS Letters

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Lipoprotein MtsA is a critical component of MtsABC responsible for iron binding and transport in the Gram-positive bacterium Streptococcus pyogenes. The present collective experimental data establish that Fe 2+ is the primary binding ion for MtsA under optimal physiologically relevant conditions. The binding affinities of MtsA to metal ions are Fe 2+ > Fe 3+ >-Cu 2+ > Mn 2+ > Zn 2+ . We report for the first time that bicarbonate is required as a synergistic anion for stable ferrous binding to MtsA, similar to the iron binding in human transferrin. This work provides valuable information, which helps to understand iron metabolism in bacteria, and creates a basis for developing strategies to suppress bacterial infection.

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“…The pK a value associated to the Tyr188 residue was recently measured by 2D NMR-pH titration as 6.9 (0.5 M KCl) [30]. Based on the Davies equation we recalculated a value of 7.2 for zero ionic strength [31] for introduction into the calculation code.…”

Section: Modelling the Binding Of U(vi) To Hstfmentioning

confidence: 99%

Spectroscopic study of the interaction of U(VI) with transferrin and albumin for speciation of U(VI) under blood serum conditions

Montavon¹,

Apostolidis²,

Bruchertseifer³

et al. 2009

Journal of Inorganic Biochemistry

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The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal-containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.

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The low pK_a value of iron‐binding ligand Tyr188 and its implication in iron release and anion binding of human transferrin

Cited by 17 publications

References 20 publications

Covalent binding of the organophosphorus agent FP-biotin to tyrosine in eight proteins that have no active site serine

Covalent binding of the organophosphorus agent FP-biotin to tyrosine in eight proteins that have no active site serine

Lipoprotein MtsA of MtsABC in Streptococcus pyogenes primarily binds ferrous ion with bicarbonate as a synergistic anion

Spectroscopic study of the interaction of U(VI) with transferrin and albumin for speciation of U(VI) under blood serum conditions

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The low pKa value of iron‐binding ligand Tyr188 and its implication in iron release and anion binding of human transferrin

Cited by 17 publications

References 20 publications

Covalent binding of the organophosphorus agent FP-biotin to tyrosine in eight proteins that have no active site serine

Covalent binding of the organophosphorus agent FP-biotin to tyrosine in eight proteins that have no active site serine

Lipoprotein MtsA of MtsABC in Streptococcus pyogenes primarily binds ferrous ion with bicarbonate as a synergistic anion

Spectroscopic study of the interaction of U(VI) with transferrin and albumin for speciation of U(VI) under blood serum conditions

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The low pK_a value of iron‐binding ligand Tyr188 and its implication in iron release and anion binding of human transferrin