Biochem J 169(3): 509-516
The binding of porphyrins by ligandin.
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.
Full text
Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brown SB, Shillcock M, Jones P. Equilibrium and kinetic studies of the aggregation of porphyrins in aqueous solution. Biochem J. 1976 Feb 1;153(2):279–285.[PMC free article] [PubMed] [Google Scholar]
- Gallagher WA, Elliott WB. Ligand-binding in porphyrin systems. Ann N Y Acad Sci. 1973;206:463–482. [PubMed] [Google Scholar]
- GIBSON QH. THE COMBINATION OF PORPHYRINS WITH NATIVE HUMAN GLOBIN. J Biol Chem. 1964 Oct;239:3282–3287. [PubMed] [Google Scholar]
- Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974 Nov 25;249(22):7130–7139. [PubMed] [Google Scholar]
- Kamisaka K, Listowsky I, Arias IM. 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 Nov 26;226:148–153. [PubMed] [Google Scholar]
- Kamisaka K, Listowsky I, Gatmaitan Z, Arias IM. Interactions of bilirubin and other ligands with ligandin. Biochemistry. 1975 May 20;14(10):2175–2180. [PubMed] [Google Scholar]
- Ketley JN, Habig WH, Jakoby WB. Binding of nonsubstrate ligands to the glutathione S-transferases. J Biol Chem. 1975 Nov 25;250(22):8670–8673. [PubMed] [Google Scholar]
- Ketterer B, Tipping E, Meuwissen J, Beale D. Ligandin. Biochem Soc Trans. 1975;3(5):626–630. [PubMed] [Google Scholar]
- Ketterer B, Tipping E, Hackney JF, Beale D. A low-molecular-weight protein from rat liver that resembles ligandin in its binding properties. Biochem J. 1976 Jun 1;155(3):511–521.[PMC free article] [PubMed] [Google Scholar]
- Koskelo P, Toivonen I. Separation of urinary coproporphyrin isomers 1 and 3 by thin-layer chromatography. Studies in healthy subjects and patients with myocardial infarction. Scand J Clin Lab Invest. 1966;18(5):543–549. [PubMed] [Google Scholar]
- Koskelo P, Toivonen I. Preparation of 14C-labeled series I and 3 porphyrins. Clin Chem. 1970 Jun;16(6):459–461. [PubMed] [Google Scholar]
- Levi AJ, Gatmaitan Z, Arias IM. 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 Nov;48(11):2156–2167.[PMC free article] [PubMed] [Google Scholar]
- Litwack G, Ketterer B, Arias IM. Ligandin: a hepatic protein which binds steroids, bilirubin, carcinogens and a number of exogenous organic anions. Nature. 1971 Dec 24;234(5330):466–467. [PubMed] [Google Scholar]
- LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- MAEHLY AC. Haemin-protein binding in peroxidase and methaemalbumin. Nature. 1961 Nov 18;192:630–632. [PubMed] [Google Scholar]
- Meuwissen JA, Ketterer B, Heirwegh KP, de Groote J. Ligandin. Tijdschr Gastroenterol. 1975;18(1):7–20. [PubMed] [Google Scholar]
- Pasternack RF, Huber PR, Boyd P, Engasser G, Francesconi L, Gibbs E, Fasella P, Venturo GC, Hinds L de C. On the aggregation of meso-substituted water-soluble porphyrins. J Am Chem Soc. 1972 Jun 28;94(13):4511–4517. [PubMed] [Google Scholar]
- 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 Jul 1;157(1):211–216.[PMC free article] [PubMed] [Google Scholar]
- Tipping E, Ketterer B, Christodoulides L, Enderby G. The interactions of haem with ligandin and aminoazo-dye-binding protein A. Biochem J. 1976 Aug 1;157(2):461–467.[PMC free article] [PubMed] [Google Scholar]
- 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 Aug 16;67(2):583–590. [PubMed] [Google Scholar]
- Woolley PV, 3rd, Hunter MJ, Arias IM. Bilirubin and biliverdin binding to rat Y protein (ligandin). Biochim Biophys Acta. 1976 Sep 28;446(1):115–123. [PubMed] [Google Scholar]