Solution structures by 1 H NMR of the novel cyclic trypsin inhibitor SFTI-1 from sunflower seeds and an acyclic permutant 1 1Edited by M. F. Summers

Korsinczky, Michael L. J.; Schirra, Horst Joachim; Rosengren, K. Johan; West, Jenny; Condie, Barry A.; Ötvös, László; Anderson, Marilyn A.; Craik, David J.

doi:10.1006/jmbi.2001.4887

Cited by 217 publications

(396 citation statements)

References 30 publications

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“…The isothermal titration calorimetric data confirmed the prior knowledge [5,20] that the stoichiometry of the resulting inhibitor-trypsin complexes equals 1:1 (SFTI-1/ enzyme). The fully exposed binding loop of the bicyclic SFTI-1 possesses only one P 1 -P 1 0 reactive site with Lys residue in the P 1 position that is mainly responsible for interactions with the enzyme.…”

Section: Resultssupporting

confidence: 78%

Interactions between trypsin and its peptidic inhibitors studied by isothermal titration calorimetry (ITC)

Dębowski

Wyrzykowski

Lubos

et al. 2015

J Therm Anal Calorim

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Isothermal titration calorimetry (ITC) technique was used to study the interactions of trypsin with bicyclic sunflower-derived trypsin inhibitor (SFTI-1) as well as with its new monocyclic (with disulphide bridge only) analogues (C 3 H 5 O)-SFTI-1 and (C 8 H 15 O)-SFTI-1. ITC measurements were run in 50 mM buffer solution of HEPES or Tricine of pH 8, containing 20 mM CaCl 2 at 298.15 K. Based on calorimetric data, the equilibrium constants for the inhibitor-enzyme-binding processes, K, the binding stoichiometry, N (inhibitor-to-enzyme molar ratio), as well as thermodynamic parameters (DG, DH, DS) for the reactions were determined. The study revealed that the stoichiometry of the resulting complexes equals 1:1. The negative binding enthalpy (D ITC H) and favourable entropy factor (TD ITC S) suggest an important contribution of hydrogen bonding as well as hydrophobic interactions to the inhibitor-enzyme affinity. Furthermore, the relationship between the modification of the peptide structure, the experimental conditions and the thermodynamic parameters has been discussed.

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Section: Resultssupporting

confidence: 78%

Interactions between trypsin and its peptidic inhibitors studied by isothermal titration calorimetry (ITC)

Dębowski

Wyrzykowski

Lubos

et al. 2015

J Therm Anal Calorim

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“…The crystal structure of the free MASP-2 enzyme (40) showed that in the absence of bound substrate or inhibitor, the substrate binding groove on the enzyme is largely obstructed by long surface loops. Lacking structural information about the positions of these loops in a complex, we decided to design the library based on the smallest known natural trypsin inhibitor scaffold of the SFTI (27)(28)(29)(30).…”

Section: Design and Construction Of The Inhibitory Peptide-phage Librarymentioning

confidence: 99%

“…Our target proteases were the MASP-1 and MASP-2, the initiator proteases of the lectin pathway. As a starting point for inhibitor selection, we used the sunflower trypsin inhibitor (SFTI), which has the shortest scaffold (only 14 aa) among the known natural SP inhibitors (27)(28)(29)(30). The selected peptides inhibit exclusively the lectin pathway among the three activation pathways of complement.…”

mentioning

confidence: 99%

Selective Inhibition of the Lectin Pathway of Complement with Phage Display Selected Peptides against Mannose-Binding Lectin-Associated Serine Protease (MASP)-1 and -2: Significant Contribution of MASP-1 to Lectin Pathway Activation

Kocsis

Kékesi

Szász

et al. 2010

The Journal of Immunology

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The complement system, an essential part of the innate immune system, can be activated through three distinct routes: the classical, the alternative, and the lectin pathways. The contribution of individual activation pathways to different biological processes can be assessed by using pathway-selective inhibitors. In this paper, we report lectin pathway-specific short peptide inhibitors developed by phage display against mannose-binding lectin-associated serine proteases (MASPs), MASP-1 and MASP-2. On the basis of the selected peptide sequences, two 14-mer peptides, designated as sunflower MASP inhibitor (SFMI)-1 and SFMI-2, were produced and characterized. SFMI-1 inhibits both MASP-1 and MASP-2 with a KI of 65 and 1030 nM, respectively, whereas SFMI-2 inhibits only MASP-2 with a KI of 180 nM. Both peptides block the lectin pathway activation completely while leaving the classical and the alternative routes intact and fully functional, demonstrating that of all complement proteases only MASP-1 and/or MASP-2 are inhibited by these peptides. In a C4 deposition inhibitor assay using preactivated MASP-2, SFMI-2 is 10-fold more effective than SFMI-1 in accordance with the fact that SFMI-2 is a more potent inhibitor of MASP-2. Surprisingly, however, out of the two peptides, SFMI-1 is much more effective in preventing C3 and C4 deposition when normal human serum containing zymogen MASPs is used. This suggests that MASP-1 has a crucial role in the initiation steps of lectin pathway activation most probably by activating MASP-2. Because the lectin pathway has been implicated in several life-threatening pathological states, these inhibitors should be considered as lead compounds toward developing lectin pathway blocking therapeutics.

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“…The latter is derived from the cotranslational processing of two related genes by a mechanism that is not yet known, and the biosynthetic origin of the former is unknown. We have recently reported the structures of both these molecules (14,15).…”

mentioning

confidence: 99%

Biosynthesis and insecticidal properties of plant cyclotides: The cyclic knotted proteins from Oldenlandia affinis

Jennings

West

Waine

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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469

679

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Several members of the Rubiaceae and Violaceae families produce a series of cyclotides or macrocyclic peptides of 29 -31 amino acids with an embedded cystine knot. We aim to understand the mechanism of synthesis of cyclic peptides in plants and have isolated a cDNA clone that encodes the cyclotide kalata B1 as well as three other clones for related cyclotides from the African plant Oldenlandia affinis. The cDNA clones encode prepropeptides with a 20-aa signal sequence, an N-terminal prosequence of 46 -68 amino acids and one, two, or three cyclotide domains separated by regions of about 25 aa. The corresponding cyclotides have been isolated from plant material, indicating that the cyclotide domains are excised and cyclized from all four predicted precursor proteins. The exact processing site is likely to lie on the N-terminal side of the strongly conserved GlyLeuPro or SerLeuPro sequence that flanks both sides of the cyclotide domain. Cyclotides have previously been assigned an antimicrobial function; here we describe a potent inhibitory effect on the growth and development of larvae from the Lepidopteran species Helicoverpa punctigera.

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Solution structures by 1 H NMR of the novel cyclic trypsin inhibitor SFTI-1 from sunflower seeds and an acyclic permutant 1 1Edited by M. F. Summers

Cited by 217 publications

References 30 publications

Interactions between trypsin and its peptidic inhibitors studied by isothermal titration calorimetry (ITC)

Interactions between trypsin and its peptidic inhibitors studied by isothermal titration calorimetry (ITC)

Selective Inhibition of the Lectin Pathway of Complement with Phage Display Selected Peptides against Mannose-Binding Lectin-Associated Serine Protease (MASP)-1 and -2: Significant Contribution of MASP-1 to Lectin Pathway Activation

Biosynthesis and insecticidal properties of plant cyclotides: The cyclic knotted proteins from Oldenlandia affinis

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