Dual Role of Lys206−Lys296 Interaction in Human Transferrin N-Lobe:  Iron-Release Trigger and Anion-Binding Site†

Biochemistry ◽  
1999 ◽  
Vol 38 (30) ◽  
pp. 9704-9711 ◽  
Author(s):  
Qing-Yu He ◽  
Anne B. Mason ◽  
Beatrice M. Tam ◽  
Ross T. A. MacGillivray ◽  
Robert C. Woodworth
Keyword(s):  
Binding Site ◽  
Dual Role ◽  
Anion Binding ◽  
Iron Release ◽  
Human Transferrin

scholarly journals The low pKavalue of iron-binding ligand Tyr188 and its implication in iron release and anion binding of human transferrin

FEBS Letters ◽  
2004 ◽  
Vol 573 (1-3) ◽  
pp. 181-185 ◽  
Author(s):  
Xuesong Sun ◽  
Hongzhe Sun ◽  
Ruiguang Ge ◽  
Megan Richter ◽  
Robert C. Woodworth ◽  
...  
Keyword(s):  
Anion Binding ◽  
Iron Binding ◽  
Iron Release ◽  
Human Transferrin

scholarly journals The chloride effect is related to anion binding in determining the rate of iron release from the human transferrin N-lobe

2000 ◽  
Vol 350 (3) ◽  
pp. 909-915 ◽  
Author(s):  
Qing-Yu HE ◽  
Anne B. MASON ◽  
Vinh NGUYEN ◽  
Ross T. A. MacGILLIVRAY ◽  
Robert C. WOODWORTH
Keyword(s):  
Low Ph ◽  
Anion Binding ◽  
Iron Release ◽  
Mutant Proteins ◽  
Major Function ◽  
Anion Effect ◽  
Human Transferrin ◽  
Binding Residue ◽  
Chloride Effect

The major function of human transferrin is to deliver iron from the bloodstream to actively dividing cells. Upon iron release, the protein changes its conformation from ‘closed’ to ‘open’. Extensive studies in vitro indicate that iron release from transferrin is very complex and involves many factors, including pH, the chelator used, an anion effect, temperature, receptor binding and intra-lobe interactions. Our earlier work [He, Mason and Woodworth (1997) Biochem. J. 328, 439–445] using the isolated transferrin N-lobe (recombinant N-lobe of human transferrin comprising residues 1–337; hTF/2N) has shown that anions and pH modulate iron release from hTF/2N in an interdependent manner: chloride retards iron release at neutral pH, but accelerates the reaction at acidic pH. The present study supports this idea and further details the nature of the dual effect of chloride: the anion effect on iron release is closely related to the strength of anion binding to the apoprotein. The negative effect seems to originate from competition between chloride and the chelator for an anion-binding site(s) near the metal centre. With decreasing pH, the strength of anion binding to hTF/2N increases linearly, decreasing the contribution of competition with the chelator. In the meantime, the ‘open’ or ‘loose’ conformation of hTF/2N, induced by the protonation of critical residues such as the Lys-206/Lys-296 pair at low pH, enables chloride to enter the cleft and bind to exposed side chains, thereby promoting cleft opening and synergistically allowing removal of iron by the chelator, leading to a positive anion effect. Disabling one or more of the primary anion-binding residues, namely Arg-124, Lys-206 and Lys-296, substantially decreases the anion-binding ability of the resulting mutant proteins. In these cases, the competition for the remaining binding residue(s) is increased, leading to a negative chloride effect or, at most, a very small positive effect, even at low pH.

scholarly journals Role of the Anion-Binding Site in Catalysis and Regulation ofMycobacterium tuberculosisd-3-Phosphoglycerate Dehydrogenase

Biochemistry ◽  
2009 ◽  
Vol 48 (22) ◽  
pp. 4808-4815 ◽  
Author(s):  
Rodney L. Burton ◽  
Shawei Chen ◽  
Xiao Lan Xu ◽  
Gregory A. Grant
Keyword(s):  
Binding Site ◽  
Anion Binding ◽  
Phosphoglycerate Dehydrogenase

scholarly journals The chloride effect is related to anion binding in determining the rate of iron release from the human transferrin N-lobe

2000 ◽  
Vol 350 (3) ◽  
pp. 909 ◽  
Author(s):  
Qing-Yu HE ◽  
Anne B. MASON ◽  
Vinh NGUYEN ◽  
Ross T.A. MacGILLIVRAY ◽  
Robert C. WOODWORTH
Keyword(s):  
Anion Binding ◽  
Iron Release ◽  
Human Transferrin ◽  
Chloride Effect

scholarly journals ROLE OF HEPATIC ANION-BINDING PROTEIN IN BROMSULPHTHALEIN CONJUGATION

1973 ◽  
Vol 138 (2) ◽  
pp. 483-487 ◽  
Author(s):  
N. Kaplowitz ◽  
I. W. Percy-Robb ◽  
N. B. Javitt
Keyword(s):  
Soluble Protein ◽  
Gel Filtration ◽  
Dual Role ◽  
Anion Binding ◽  
Sensitive Assay ◽  
Transport Function ◽  
Hepatic Transport ◽  
Highly Sensitive ◽  
Intracellular Binding

Using gel filtration, the binding of both glutathione and Bromsulphthalein (BSP) to a liver-soluble protein was found to be identical. BSP-conjugating activity (glutathione S-aryltransferase) was present only in the fractions corresponding to the two protein-bound markers. Using a highly sensitive assay, with 3,4-dichloronitrobenzene, the pattern of glutathione S-aryltransferase activity was found to coincide with Y protein. This evidence suggests that Y protein, or ligandin, has a dual role in hepatic transport: a specific enzymic function in the conjugation of certain anions with glutathione in addition to a transport function in the intracellular binding of organic anions.

Sign in / Sign up

Export Citation Format

Share Document