The Binding of Porphyrins by Ligandin

Overview

Journal Biochem J

Specialty Biochemistry

Date 1978 Mar 1

PMID 646788

Citations 13

Authors

E Tipping

B Ketterer

P KOSKELO

Affiliations

Soon will be listed here.

Abstract

Spectrophotometric and equilibrium-dialysis measurements show that ligandin (glutathione S-transferase B, EC 2.5.1.18) binds monomeric porphyrins at a single site with association constants in the range 10(4)-10(6) litre/mol at pH 7.0. Binding affinities are paralleled by the tendencies of the porphyrins to aggregate, increasing in the order: uroporphyrins I and III less than coproporphyrins I and III approximately haematoporphyrin less than protoporphyrin IX. From this it is deduced that the hydrophobic effect is the predominant driving-force for binding. The porphyrins can be displaced from their binding site on ligandin by bromosulphophthalein and oestrone sulphate. In enzyme inhibition studies, 50% inhibition was brought about by 8 micron-haematoporphyrin and by 1 micron-protoporphyrin IX. In the analysis of the haemotoporphyrin-ligandin system the self-association of haematoporphyrin was studied in detail. It was found to be limited to dimerization in the concentration range 0-200 micron at pH 7.0, 25 degrees C and a dimerization constant of 1.9 x 10(5) litre/mol was determined. Coproporphrin III has a dimerization constant of 5.2 x 10(5) litre/mol under the same conditions.

Citing Articles

The auxiliary [4Fe-4S] cluster of the Radical SAM heme synthase from is involved in electron transfer.

Kuhner M, Schweyen P, Hoffmann M, Vazquez Ramos J, Reijerse E, Lubitz W Chem Sci. 2018; 7(7):4633-4643.

PMID: 30155111 PMC: 6013774. DOI: 10.1039/c6sc01140c.

One ring to rule them all: trafficking of heme and heme synthesis intermediates in the metazoans.

Hamza I, Dailey H Biochim Biophys Acta. 2012; 1823(9):1617-32.

PMID: 22575458 PMC: 3412874. DOI: 10.1016/j.bbamcr.2012.04.009.

Glutathione S-transferase P1-1 expression modulates sensitivity of human kidney 293 cells to photodynamic therapy with hypericin.

Dabrowski M, Maeda D, Zebala J, Lu W, Mahajan S, Kavanagh T Arch Biochem Biophys. 2006; 449(1-2):94-103.

PMID: 16546115 PMC: 4437720. DOI: 10.1016/j.abb.2006.02.009.

The role of glutathione-S-transferase in anti-cancer drug resistance.

Townsend D, Tew K Oncogene. 2003; 22(47):7369-75.

PMID: 14576844 PMC: 6361125. DOI: 10.1038/sj.onc.1206940.

The influence of soluble binding proteins on lipophile transport and metabolism in hepatocytes.

Tipping E, Ketterer B Biochem J. 1981; 195(2):441-52.

PMID: 7316961 PMC: 1162908. DOI: 10.1042/bj1950441.

References

MAEHLY A . Haemin-protein binding in peroxidase and methaemalbumin. Nature. 1961; 192:630-2. DOI: 10.1038/192630a0. View

GIBSON Q . THE COMBINATION OF PORPHYRINS WITH NATIVE HUMAN GLOBIN. J Biol Chem. 1964; 239:3282-7. View

LOWRY O, ROSEBROUGH N, FARR A, RANDALL R . Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1):265-75. View

Tipping E, Ketterer B, Christodoulides L, ENDERBY G . The non-convalent binding of small molecules by ligandin. Interactions with steroids and their conjugates, fatty acids, bromosulphophthalein carcinogens, glutathione and realted compounds. Eur J Biochem. 1976; 67(2):583-90. DOI: 10.1111/j.1432-1033.1976.tb10724.x. View

WOOLLEY 3rd P, Hunter M, Arias I . Bilirubin and biliverdin binding to rat Y protein (ligandin). Biochim Biophys Acta. 1976; 446(1):115-23. DOI: 10.1016/0005-2795(76)90103-3. View

Ketterer B, Tipping E, Meuwissen J, Beale D . Ligandin. Biochem Soc Trans. 1975; 3(5):626-30. DOI: 10.1042/bst0030626. View

Gallagher W, Elliott W . Ligand-binding in porphyrin systems. Ann N Y Acad Sci. 1973; 206:463-82. DOI: 10.1111/j.1749-6632.1973.tb43230.x. View

Tipping E, Ketterer B, Christodoulides L, ENDERBY G . The interactions of haem with ligandin and aminoazo-dye-binding protein A. Biochem J. 1976; 157(2):461-7. PMC: 1163873. DOI: 10.1042/bj1570461. View

Tipping E, Ketterer B, Christodoulides L, ENDERBY G . Spectroscopic studies of the binding of bilirubin by ligandin and aminoazo-dye-binding protein A. Biochem J. 1976; 157(1):211-6. PMC: 1163833. DOI: 10.1042/bj1570211. View

10.

Ketterer B, Tipping E, HACKNEY J, Beale D . A low-molecular-weight protein from rat liver that resembles ligandin in its binding properties. Biochem J. 1976; 155(3):511-21. PMC: 1172873. DOI: 10.1042/bj1550511. View

11.

Ketley J, Habig W, Jakoby W . Binding of nonsubstrate ligands to the glutathione S-transferases. J Biol Chem. 1975; 250(22):8670-3. View

12.

Kamisaka K, Listowsky I, GATMAITAN Z, Arias I . Interactions of bilirubin and other ligands with ligandin. Biochemistry. 1975; 14(10):2175-80. DOI: 10.1021/bi00681a021. View

13.

Meuwissen J, Ketterer B, Heirwegh K, De Groote J . Ligandin. Tijdschr Gastroenterol. 1975; 18(1):7-20. View

14.

Brown S, Shillcock M, Jones P . Equilibrium and kinetic studies of the aggregation of porphyrins in aqueous solution. Biochem J. 1976; 153(2):279-85. PMC: 1172573. DOI: 10.1042/bj1530279. View

15.

Kamisaka K, Listowsky I, Arias I . Circular dichroism studies of Y protein (ligandin), a major organic anion binding protein in liver, kidney, and small intestine. Ann N Y Acad Sci. 1973; 226:148-53. DOI: 10.1111/j.1749-6632.1973.tb20477.x. View

16.

Habig W, Pabst M, Jakoby W . Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974; 249(22):7130-9. View

17.

Pasternack R, HUBER P, Boyd P, Engasser G, Francesconi L, Gibbs E . On the aggregation of meso-substituted water-soluble porphyrins. J Am Chem Soc. 1972; 94(13):4511-7. DOI: 10.1021/ja00768a016. View

18.

Levi A, GATMAITAN Z, Arias I . Two hepatic cytoplasmic protein fractions, Y and Z, and their possible role in the hepatic uptake of bilirubin, sulfobromophthalein, and other anions. J Clin Invest. 1969; 48(11):2156-67. PMC: 297469. DOI: 10.1172/JCI106182. View

19.

Litwack G, Ketterer B, Arias I . Ligandin: a hepatic protein which binds steroids, bilirubin, carcinogens and a number of exogenous organic anions. Nature. 1971; 234(5330):466-7. DOI: 10.1038/234466a0. View

20.

KOSKELO P, Toivonen I . Preparation of 14C-labeled series I and 3 porphyrins. Clin Chem. 1970; 16(6):459-61. View