Reformable intramolecular cross-linking of the N-terminal domain of heparin cofactor II - Effects on enzyme inhibition

Brinkmeyer S, Eckert R, Ragg H (2004)
EUROPEAN JOURNAL OF BIOCHEMISTRY 271(21): 4275-4283.

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Zeitschriftenaufsatz | Veröffentlicht | Englisch
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Abstract / Bemerkung
The crystal structure of a heparin cofactor II (HCII)-thrombin Michaelis complex has revealed extensive contacts encompassing the N-terminal domain of HCII and exosite I of the proteinase. In contrast, the location of the N-terminal extension in the uncomplexed inhibitor was unclear. Using a disulfide cross-linking strategy, we demonstrate that at least three different sites (positions 52, 54 and 68) within the N terminus may be tethered in a reformable manner to position 195 in the loop region between helix D and strand s2A of the HCII molecule, suggesting that the N-terminal domain may interact with the inhibitor scaffold in a permissive manner. Cross-linking of the N terminus to the HCII body does not strongly affect the inhibition of alpha-chymotrypsin, indicating that the reactive site loop sequences of the engineered inhibitor variants, required for interaction with one of the HCII target enzymes, are normally accessible. In contrast, intramolecular tethering of the N-terminal extension results in a drastic decrease of alpha-thrombin inhibitory activity, both in the presence and in the absence of glycosaminoglycans. Treatment with dithiothreitol and iodoacetamide restores activity towards alpha-thrombin, suggesting that release of the N terminus of HCII is an important component of the multistep interaction between the inhibitor and alpha-thrombin.
Erscheinungsjahr
Zeitschriftentitel
EUROPEAN JOURNAL OF BIOCHEMISTRY
Band
271
Zeitschriftennummer
21
Seite
4275-4283
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Brinkmeyer S, Eckert R, Ragg H. Reformable intramolecular cross-linking of the N-terminal domain of heparin cofactor II - Effects on enzyme inhibition. EUROPEAN JOURNAL OF BIOCHEMISTRY. 2004;271(21):4275-4283.
Brinkmeyer, S., Eckert, R., & Ragg, H. (2004). Reformable intramolecular cross-linking of the N-terminal domain of heparin cofactor II - Effects on enzyme inhibition. EUROPEAN JOURNAL OF BIOCHEMISTRY, 271(21), 4275-4283. doi:10.1111/j.1432-1033.2004.04367.x
Brinkmeyer, S., Eckert, R., and Ragg, H. (2004). Reformable intramolecular cross-linking of the N-terminal domain of heparin cofactor II - Effects on enzyme inhibition. EUROPEAN JOURNAL OF BIOCHEMISTRY 271, 4275-4283.
Brinkmeyer, S., Eckert, R., & Ragg, H., 2004. Reformable intramolecular cross-linking of the N-terminal domain of heparin cofactor II - Effects on enzyme inhibition. EUROPEAN JOURNAL OF BIOCHEMISTRY, 271(21), p 4275-4283.
S. Brinkmeyer, R. Eckert, and H. Ragg, “Reformable intramolecular cross-linking of the N-terminal domain of heparin cofactor II - Effects on enzyme inhibition”, EUROPEAN JOURNAL OF BIOCHEMISTRY, vol. 271, 2004, pp. 4275-4283.
Brinkmeyer, S., Eckert, R., Ragg, H.: Reformable intramolecular cross-linking of the N-terminal domain of heparin cofactor II - Effects on enzyme inhibition. EUROPEAN JOURNAL OF BIOCHEMISTRY. 271, 4275-4283 (2004).
Brinkmeyer, Stephan, Eckert, Ralf, and Ragg, Hermann. “Reformable intramolecular cross-linking of the N-terminal domain of heparin cofactor II - Effects on enzyme inhibition”. EUROPEAN JOURNAL OF BIOCHEMISTRY 271.21 (2004): 4275-4283.

9 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

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PMID: 21722639
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PMID: 21972922
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PMID: 17194895
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42 References

Daten bereitgestellt von Europe PubMed Central.

Heparin cofactor II.
Tollefsen DM., Adv. Exp. Med. Biol. 425(), 1997
PMID: 9433487
Inhibition of chymotrypsin by heparin cofactor II.
Church FC, Noyes CM, Griffith MJ., Proc. Natl. Acad. Sci. U.S.A. 82(19), 1985
PMID: 3863104
The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature.
Silverman GA, Bird PI, Carrell RW, Church FC, Coughlin PB, Gettins PG, Irving JA, Lomas DA, Luke CJ, Moyer RW, Pemberton PA, Remold-O'Donnell E, Salvesen GS, Travis J, Whisstock JC., J. Biol. Chem. 276(36), 2001
PMID: 11435447
Serpin structure, mechanism, and function.
Gettins PG., Chem. Rev. 102(12), 2002
PMID: 12475206
Structure of a serpin-protease complex shows inhibition by deformation.
Huntington JA, Read RJ, Carrell RW., Nature 407(6806), 2000
PMID: 11057674
On the activation of human leuserpin-2, a thrombin inhibitor, by glycosaminoglycans.
Ragg H, Ulshofer T, Gerewitz J., J. Biol. Chem. 265(9), 1990
PMID: 2318889
Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism.
Baglin TP, Carrell RW, Church FC, Esmon CT, Huntington JA., Proc. Natl. Acad. Sci. U.S.A. 99(17), 2002
PMID: 12169660
A new member of the plasma protease inhibitor gene family.
Ragg H., Nucleic Acids Res. 14(2), 1986
PMID: 3003690
Comparison of heparin- and dermatan sulfate-mediated catalysis of thrombin inactivation by heparin cofactor II.
Liaw PC, Austin RC, Fredenburgh JC, Stafford AR, Weitz JI., J. Biol. Chem. 274(39), 1999
PMID: 10488098
Role of thrombin anion-binding exosite-I in the formation of thrombin-serpin complexes.
Myles T, Church FC, Whinna HC, Monard D, Stone SR., J. Biol. Chem. 273(47), 1998
PMID: 9813026
A rapid and efficient one-tube PCR-based mutagenesis technique using Pfu DNA polymerase.
Picard V, Ersdal-Badju E, Lu A, Bock SC., Nucleic Acids Res. 22(13), 1994
PMID: 8041621
A one-step purification of membrane proteins using a high efficiency immunomatrix.
Schneider C, Newman RA, Sutherland DR, Asser U, Greaves MF., J. Biol. Chem. 257(18), 1982
PMID: 6955305
Renaturation of human proinsulin--a study on refolding and conversion to insulin.
Winter J, Lilie H, Rudolph R., Anal. Biochem. 310(2), 2002
PMID: 12423632

Kellner, 1994
Active-site titration of peptidases.
Knight CG., Meth. Enzymol. 248(), 1995
PMID: 7674964
Probing protein folding and stability using disulfide bonds.
Darby N, Creighton TE., Mol. Biotechnol. 7(1), 1997
PMID: 9163722
Activation of heparin cofactor II by dermatan sulfate.
Tollefsen DM, Pestka CA, Monafo WJ., J. Biol. Chem. 258(11), 1983
PMID: 6687888
Stabilization of functional proteins by introduction of multiple disulfide bonds.
Matsumura M, Matthews BW., Meth. Enzymol. 202(), 1991
PMID: 1784181
Blocking the Ca2+-induced conformational transitions in calmodulin with disulfide bonds.
Tan RY, Mabuchi Y, Grabarek Z., J. Biol. Chem. 271(13), 1996
PMID: 8631777
Conformational changes necessary for gene regulation by Tet repressor assayed by reversible disulfide bond formation.
Tiebel B, Aung-Hilbrich LM, Schnappinger D, Hillen W., EMBO J. 17(17), 1998
PMID: 9724647
Reversibly locking a protein fold in an active conformation with a disulfide bond: integrin alphaL I domains with high affinity and antagonist activity in vivo.
Shimaoka M, Lu C, Palframan RT, von Andrian UH, McCormack A, Takagi J, Springer TA., Proc. Natl. Acad. Sci. U.S.A. 98(11), 2001
PMID: 11353828
What does it mean to be natively unfolded?
Uversky VN., Eur. J. Biochem. 269(1), 2002
PMID: 11784292
Identification of two sites of sulfation of human heparin cofactor II.
Hortin G, Tollefsen DM, Strauss AW., J. Biol. Chem. 261(34), 1986
PMID: 3782093
Glycosaminoglycan-mediated leuserpin-2/thrombin interaction. Structure-function relationships.
Ragg H, Ulshofer T, Gerewitz J., J. Biol. Chem. 265(36), 1990
PMID: 2266131
Activation of heparin cofactor II by calcium spirulan.
Hayakawa Y, Hayashi T, Lee JB, Ozawa T, Sakuragawa N., J. Biol. Chem. 275(15), 2000
PMID: 10753952

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