Interaction of Thioredoxins with Target Proteins: Role of Particular Structural Elements and Electrostatic Properties of Thioredoxins in Their Interplay with 2-oxoacid Dehydrogenase Complexes

Overview

Journal Protein Sci

Specialty Biochemistry

Date 1999 Apr 21

PMID 10210184

Citations 13

Authors

V Bunik

G Raddatz

S Lemaire

Y Meyer

J P Jacquot

H Bisswanger

Affiliations

Soon will be listed here.

Abstract

The thioredoxin action upon the 2-oxoacid dehydrogenase complexes is investigated by using different thioredoxins, both wild-type and mutated. The attacking cysteine residue of thioredoxin is established to be essential for the thioredoxin-dependent activation of the complexes. Mutation of the buried cysteine residue to serine is not crucial for the activation, but prevents inhibition of the complexes, exhibited by the Clamydomonas reinhardtii thioredoxin m disulfide. Site-directed mutagenesis of D26, W31, F/W12, and Y/A70 (the Escherichia coli thioredoxin numbering is employed for all the thioredoxins studied) indicates that both the active site and remote residues of thioredoxin are involved in its interplay with the 2-oxoacid dehydrogenase complexes. Sequences of 11 thioredoxin species tested biochemically are aligned. The thioredoxin residues at the contact between the alpha3/3(10) and alpha1 helices, the length of the alpha1 helix and the charges in the alpha2-beta3 and beta4-beta5 linkers are found to correlate with the protein influence on the 2-oxoacid dehydrogenase complexes (the secondary structural elements of thioredoxin are defined according to Eklund H et al., 1991, Proteins 11:13-28). The distribution of the charges on the surface of the thioredoxin molecules is analyzed. The analysis reveals the species specific polarization of the thioredoxin active site surroundings, which corresponds to the efficiency of the thioredoxin interplay with the 2-oxoacid dehydrogenase systems. The most effective mitochondrial thioredoxin is characterized by the strongest polarization of this area and the highest value of the electrostatic dipole vector of the molecule. Not only the magnitude, but also the orientation of the dipole vector show correlation with the thioredoxin action. The dipole direction is found to be significantly influenced by the charges of the residues 13/14, 51, and 83/85, which distinguish the activating and inhibiting thioredoxin disulfides.

Citing Articles

Thr-to-Ala Mutation Leads to a Larger Aromatic Pair and Reduced Packing Density in α1,α3-Helices during Thioredoxin Cold Adaptation.

Nguyen T, Lee C ACS Omega. 2024; 9(9):10812-10824.

PMID: 38463323 PMC: 10918799. DOI: 10.1021/acsomega.3c09806.

Molecular Basis for the Interactions of Human Thioredoxins with Their Respective Reductases.

Hossain M, Bodnar Y, Klein C, Salas C, Arner E, Gellert M Oxid Med Cell Longev. 2021; 2021:6621292.

PMID: 34122725 PMC: 8189816. DOI: 10.1155/2021/6621292.

Selective Inhibition of 2-Oxoglutarate and 2-Oxoadipate Dehydrogenases by the Phosphonate Analogs of Their 2-Oxo Acid Substrates.

Artiukhov A, Kazantsev A, Lukashev N, Bellinzoni M, Bunik V Front Chem. 2021; 8:596187.

PMID: 33511099 PMC: 7835950. DOI: 10.3389/fchem.2020.596187.

Synthetic analogues of 2-oxo acids discriminate metabolic contribution of the 2-oxoglutarate and 2-oxoadipate dehydrogenases in mammalian cells and tissues.

Artiukhov A, Grabarska A, Gumbarewicz E, Aleshin V, Kahne T, Obata T Sci Rep. 2020; 10(1):1886.

PMID: 32024885 PMC: 7002488. DOI: 10.1038/s41598-020-58701-4.

The specificity of thioredoxins and glutaredoxins is determined by electrostatic and geometric complementarity.

Berndt C, Schwenn J, Lillig C Chem Sci. 2018; 6(12):7049-7058.

PMID: 29861944 PMC: 5947528. DOI: 10.1039/c5sc01501d.

References

Williams Jr C, Allison N, Russell G, Prongay A, Arscott L, Datta S . Properties of lipoamide dehydrogenase and thioredoxin reductase from Escherichia coli altered by site-directed mutagenesis. Ann N Y Acad Sci. 1989; 573:55-65. DOI: 10.1111/j.1749-6632.1989.tb14986.x. View

Janin J . The kinetics of protein-protein recognition. Proteins. 1997; 28(2):153-61. DOI: 10.1002/(sici)1097-0134(199706)28:2<153::aid-prot4>3.0.co;2-g. View

De Pascalis A, Jelesarov I, ACKERMANN F, Koppenol W, Hirasawa M, Knaff D . Binding of ferredoxin to ferredoxin:NADP+ oxidoreductase: the role of carboxyl groups, electrostatic surface potential, and molecular dipole moment. Protein Sci. 1993; 2(7):1126-35. PMC: 2142418. DOI: 10.1002/pro.5560020707. View

Jacquot J, Stein M, Suzuki A, Liottet S, Sandoz G, Miginiac-Maslow M . Residue Glu-91 of Chlamydomonas reinhardtii ferredoxin is essential for electron transfer to ferredoxin-thioredoxin reductase. FEBS Lett. 1997; 400(3):293-6. DOI: 10.1016/s0014-5793(96)01407-x. View

Birkett D, Price N, Radda G, Salmon A . The reactivity of SH groups with a fluorogenic reagent. FEBS Lett. 1970; 6(4):346-348. DOI: 10.1016/0014-5793(70)80095-3. View

Stanley C, Perham R . Purification of 2-oxo acid dehydrogenase multienzyme complexes from ox heart by a new method. Biochem J. 1980; 191(1):147-54. PMC: 1162192. DOI: 10.1042/bj1910147. View

Buch A, Follmann H . Animal and plant mitochondria contain specific thioredoxins. FEBS Lett. 1989; 258(1):22-6. DOI: 10.1016/0014-5793(89)81606-0. View

KATTI S, Lemaster D, Eklund H . Crystal structure of thioredoxin from Escherichia coli at 1.68 A resolution. J Mol Biol. 1990; 212(1):167-84. DOI: 10.1016/0022-2836(90)90313-B. View

HOFFMAN B, Broadwater J, Johnson P, Harper J, Fox B, Kenealy W . Lactose fed-batch overexpression of recombinant metalloproteins in Escherichia coli BL21 (DE3): process control yielding high levels of metal-incorporated, soluble protein. Protein Expr Purif. 1995; 6(5):646-54. DOI: 10.1006/prep.1995.1085. View

10.

Bunik V, Follmann H . Thioredoxin reduction dependent on alpha-ketoacid oxidation by alpha-ketoacid dehydrogenase complexes. FEBS Lett. 1993; 336(2):197-200. DOI: 10.1016/0014-5793(93)80801-z. View

11.

Demchuk E, Mueller T, Oschkinat H, Sebald W, Wade R . Receptor binding properties of four-helix-bundle growth factors deduced from electrostatic analysis. Protein Sci. 1994; 3(6):920-35. PMC: 2142882. DOI: 10.1002/pro.5560030607. View

12.

Saarinen M, Gleason F, Eklund H . Crystal structure of thioredoxin-2 from Anabaena. Structure. 1995; 3(10):1097-108. DOI: 10.1016/s0969-2126(01)00245-3. View

13.

Honig B, Nicholls A . Classical electrostatics in biology and chemistry. Science. 1995; 268(5214):1144-9. DOI: 10.1126/science.7761829. View

14.

Gane P, Freedman R, Warwicker J . A molecular model for the redox potential difference between thioredoxin and DsbA, based on electrostatics calculations. J Mol Biol. 1995; 249(2):376-87. DOI: 10.1006/jmbi.1995.0303. View

15.

Holmgren A . Thioredoxin. 6. The amino acid sequence of the protein from escherichia coli B. Eur J Biochem. 1968; 6(4):475-84. DOI: 10.1111/j.1432-1033.1968.tb00470.x. View

16.

Jacquot J, Stein M, Hodges M, Miginiac-Maslow M . PCR cloning of a nucleotidic sequence coding for the mature part of Chlamydomonas reinhardtii thioredoxin Ch2. Nucleic Acids Res. 1992; 20(3):617. PMC: 310440. DOI: 10.1093/nar/20.3.617. View

17.

Eklund H, Gleason F, Holmgren A . Structural and functional relations among thioredoxins of different species. Proteins. 1991; 11(1):13-28. DOI: 10.1002/prot.340110103. View

18.

Bernstein F, Koetzle T, Williams G, Meyer Jr E, Brice M, Rodgers J . The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977; 112(3):535-42. DOI: 10.1016/s0022-2836(77)80200-3. View

19.

Lepiniec L, Hodges M, Gadal P, Cretin C . Isolation, characterization and nucleotide sequence of a full-length pea cDNA encoding thioredoxin-f. Plant Mol Biol. 1992; 18(5):1023-5. DOI: 10.1007/BF00019224. View

20.

Jacquot J, Lopez-Jaramillo J, Miginiac-Maslow M, Lemaire S, CHERFILS J, Chueca A . Cysteine-153 is required for redox regulation of pea chloroplast fructose-1,6-bisphosphatase. FEBS Lett. 1997; 401(2-3):143-7. DOI: 10.1016/s0014-5793(96)01459-7. View