Alternative Structural State of Transferrin

Mizutani, Kimihiko; Yamashita, Honami; Kurokawa, H.; Mikami, Bunzo; Hirose, Masaaki

doi:10.1074/jbc.274.15.10190

Cited by 60 publications

(26 citation statements)

References 30 publications

(19 reference statements)

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“…This implies that NTA can also act as a synergistic anion. NTA is known to be able to act as a synergistic anion in transferrins (51, 52), confirmed by the recent 2.1 Å resolution x-ray crystal structure of an Fe(III)-ovotransferrin-NTA ternary complex (53). The wavelength of the LMCT band of Fe(III)-NTA-hTF (465 nm) is the same as that for Fe(III)⅐CO 3 -hTF (52).…”

Section: Anion Binding Properties Of Nfbpsupporting

confidence: 53%

Synergistic Anion and Metal Binding to the Ferric Ion-binding Protein from Neisseria gonorrhoeae

Guo

Harvey

Yang

et al. 2003

Journal of Biological Chemistry

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The 34-kDa periplasmic iron-transport protein (FBP) from Neisseria gonorrhoeae (nFBP) contains Fe(III) and (hydrogen)phosphate (synergistic anion). It has a characteristic ligand-to-metal charge-transfer absorption band at 481 nm. Phosphate can be displaced by (bi)carbonate to give Fe⅐CO 3 ⅐nFBP ( max 459 nm). The local structures of native Fe-PO 4 -nFBP and Fe⅐CO 3 ⅐nFBP were determined by EXAFS at the FeK edge using full multiple scattering analysis. The EXAFS analysis reveals that both phosphate and carbonate ligands bind to FBP in monodentate mode in contrast to transferrins, which bind carbonate in bidentate mode. The EXAFS analysis also suggests an alternative to the crystallographically determined position of the Glu ligand, and this in turn suggests that an H-bonding network may help to stabilize monodentate binding of the synergistic anion. The anions oxalate, pyrophosphate, and nitrilotriacetate also appear to serve as synergistic anions but not sulfate or perchlorate. The oxidation of Fe(II) in the presence of nFBP led to a weak Fe(III)⅐nFBP complex ( max 471 nm). Iron and phosphate can be removed from FBP at low pH (pH 4.5) in the presence of a large excess of citrate. Apo-FBP is less soluble and less stable than Fe⅐nFBP and binds relatively weakly to Ga(III) and Bi(III) but not to Co(III) ions, all of which bind strongly to apo-human serum transferrin.

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Section: Anion Binding Properties Of Nfbpsupporting

confidence: 53%

Synergistic Anion and Metal Binding to the Ferric Ion-binding Protein from Neisseria gonorrhoeae

Guo

Harvey

Yang

et al. 2003

Journal of Biological Chemistry

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“…In the N lobe of sTfs, a pair of hydrogen-bonded lysines close to the iron center provides another pH-sensitive site; protonation of this ''dilysine pair'' would promote domain opening because the two residues are from opposing domains and should repel one another when both are charged (28)(29)(30) (31,32), and structural arguments support this (5). Once the anion has bound to the apoprotein, four of the six iron ligands (two carbonate oxygens and two tyrosines) will be associated together on one domain, and it is reasonable to suppose that this is the site of initial iron binding; indeed such intermediates have been defined crystallographically (33,34). How, then, do domain closure and coordination to the other two ligands (Asp and His) occur, given that the latter are 9-10 Å away, on the other domain?…”

Section: Transferrins: Scavengers and Distributors Of Ferric Ironmentioning

confidence: 99%

Dealing with iron: Common structural principles in proteins that transport iron and heme

Baker

Anderson

Baker

2003

Proc. Natl. Acad. Sci. U.S.A.

217

143

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Iron is essential to life, but poses severe problems because of its toxicity and the insolubility of hydrated ferric ions at neutral pH. In animals, a family of proteins called transferrins are responsible for the sequestration, transport, and distribution of free iron. Comparison of the structure and function of transferrins with a completely unrelated protein hemopexin, which carries out the same function for heme, identifies molecular features that contribute to a successful protein system for iron acquisition, transport, and release. These include a two-domain protein structure with flexible hinges that allow these domains to enclose the bound ligand and provide suitable chemistry for stable binding and an appropriate trigger for release.

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“…The structures are the holo form (15), an intermediate form (32), and the sulfate anion bound apo form (33). The apo crystal was soaked in NTA-Fe 3ϩ solution complex, which assumes an open structure but with bound iron and NTA to form an intermediate form in the iron uptake/ release process (32) …”

Section: Discussionmentioning

confidence: 99%

“…Several kinetic models were analyzed by the newly introduced method to obtain the rate constants for the quantitative evaluation of the iron release kinetics. The crystallographic structure of nonsynergistic anion bound apo N-oTf (33) along with the holo (15) and iron uptake intermediate (32) structures of N-oTf were critically analyzed to derive a mechanistic model compatible with the dual pathway kinetic mechanism.…”

mentioning

confidence: 99%

“…In this present complexity iron release kinetic mechanism of N-oTf was studied using three anions of different chemical nature: pyrophosphate, a chelator and nonsynergistic anion; NTA, a chelator and synergistic anion; and sulfate, a nonchelator and nonsynergistic anion. We have opted for isolated N-oTf because the solution and crystallographic structural details of iron binding and the intermediate complex of iron uptake are reported from this laboratory (15,(31)(32)(33). The kinetic data was obtained using the stopped flow spectrofluorimetric method at the endosomal pH of 5.6 and single anion system at a time, for the iron release process of three different anions.…”

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confidence: 99%

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Anion-mediated Iron Release from Transferrins

Muralidhara¹,

Hirose

2000

Journal of Biological Chemistry

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Iron release process of ovotransferrin N-lobe (N-oTf) to anion/chelators has been resolved using kinetic and mechanistic approach. The iron release kinetics of N-oTf were measured at the endosomal pH of 5.6 with three different anions such as nitrilotriacetate, pyrophosphate, and sulfate using stopped flow spectrofluorimetric method, all yielding clear biphasic progress curves. The two observed rate constants and the corresponding amplitudes obtained from the double exponential curve fit to the biphasic curves varied depending on the type and concentration of anions. Several possible models for the iron release kinetic mechanism were examined on the basis of a newly introduced quantitative equation. Results from the curve fitting analyses were consistent with a dual pathway mechanism that includes the competitive iron release from two different protein states, namely, X and Y, with the respective first order rate constants of K 1 and K 2 (X, domain closed holo N-oTf; Y, anion induced different conformer of holo N-oTf). The reversible interconversions of X to Y and Y to X are driven by the second order rate constant k 3 and the first order rate constant K 4 , respectively. The obtained rate constants were greatly variable for the three anions depending on the synergistic or nonsynergistic nature. In the light of the anion-binding sites of N-oTf located crystallographically, the compatible mechanistic model that includes competitive anion binding to the iron coordination sites and to a specific anion site is suggested for the dual pathway iron release mechanism.

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Alternative Structural State of Transferrin

Cited by 60 publications

References 30 publications

Synergistic Anion and Metal Binding to the Ferric Ion-binding Protein from Neisseria gonorrhoeae

Synergistic Anion and Metal Binding to the Ferric Ion-binding Protein from Neisseria gonorrhoeae

Dealing with iron: Common structural principles in proteins that transport iron and heme

Anion-mediated Iron Release from Transferrins

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