Interaction of cyclosporin A with an Fab fragment or cyclophilin Affinity measurements and time‐dependent changes in binding

Zeder‐Lutz, Gabrielle; Wenger, Roland M.; Regenmortel, M.H.V. Van; Altschuh, Danièle

doi:10.1016/0014-5793(93)81781-t

Cited by 27 publications

(17 citation statements)

References 17 publications

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“…This structure determination of . This is in contrast to CS, which requires 3045 min for complex formation with CYP [17,33] and supports the hypothesis that CS has to undergo structural changes before complex formation with CYP in a rate limiting step.…”

Section: Resultssupporting

confidence: 82%

The 3D structure of a cyclosporin analogue in water is nearly identical to the cyclophilin‐bound cyclosporin conformation

et al. 1994

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The conformation of [D-MeSe?-D-Ser-(O-Gly)*]CS, a water soluble cyclosporin derivative, has been determined in (D,)DMSO and in water using NMR. In these polar solvents the conformation is identical and very similar to the structure found in the cyclophilin-cyclosporin complex. However, it differs significantly from its conformation in deuterated chloroform. This demonstrates unambiguously that the large structure change is induced primarily by the polar solvent rather than by complex formation with cyclophilin.

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Section: Resultssupporting

confidence: 82%

The 3D structure of a cyclosporin analogue in water is nearly identical to the cyclophilin‐bound cyclosporin conformation

et al. 1994

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“…The possibility that Compstatin undergoes a structural reorientation upon binding remains open. The occurrence of conformational changes in peptides upon binding has been reported for cyclosporine complexed to cyclophilin (39,40) and for the Bak peptide complexed to the antiapoptotic protein Bcl-x L (41). To determine whether our data supported this possibility, we tried to fit our data to a two-state conformational change model (A ϩ B 7 AB 7 AB*).…”

Section: Binding Of Compstatin To C3mentioning

confidence: 99%

Binding Kinetics, Structure-Activity Relationship, and Biotransformation of the Complement Inhibitor Compstatin

Sahu

Soulika

Morikis

et al. 2000

The Journal of Immunology

102

178

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We have previously identified a 13-residue cyclic peptide, Compstatin, that binds to complement component C3 and inhibits complement activation. Herein, we describe the binding kinetics, structure-activity relationship, and biotransformation of Compstatin. Biomolecular interaction analysis using surface-plasmon resonance showed that Compstatin bound to native C3 and its fragments C3b and C3c, but not C3d. While binding of Compstatin to native C3 was biphasic, binding to C3b and C3c followed the 1:1 Langmuir binding model; the affinities of Compstatin for C3b and C3c were 22- and 74-fold lower, respectively, than that of native C3. Analysis of Compstatin analogs synthesized for structure-function studies indicated that 1) the 11-membered ring between disulfide-linked Cys2-Cys12 constitutes a minimal structure required for optimal activity; 2) retro-inverso isomerization results in loss of inhibitory activity; and 3) some residues of the type I β-turn segment also interact with C3. In vitro studies of Compstatin in human blood indicated that a major pathway of biotransformation was the removal of Ile1, which could be blocked by N-acetylation of the peptide. These findings indicate that acetylated Compstatin is stable against enzymatic degradation and that the type I β-turn segment is not only critical for preservation of the conformational stability, but also involved in intermolecular recognition.

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“…on May 9, 2018 by guest http://jb.asm.org/ these experimental conditions (33). An equilibrium dissociation constant in the nanomolar range (0.5 Ϯ 3.6 nM) was evaluated for the NP-Pvd-Fe interaction with FpvA, and since Pvd-Fe and the amine derivative have very similar binding profiles (Fig.…”

Section: Vol 190 2008mentioning

confidence: 99%

The Metal Dependence of Pyoverdine Interactions with Its Outer Membrane Receptor FpvA

Greenwald

Zeder‐Lutz

Hagège³

et al. 2008

J Bacteriol

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To acquire iron, Pseudomonas aeruginosa secretes the fluorescent siderophore pyoverdine (Pvd), which chelates iron and shuttles it into the cells via the specific outer membrane transporter FpvA. We studied the role of iron and other metals in the binding and transport of Pvd by FpvA and conclude that there is no significant affinity between FpvA and metal-free Pvd. We found that the fluorescent in vivo complex of iron-free FpvA-Pvd is in fact a complex with aluminum (FpvA-Pvd-Al) formed from trace aluminum in the growth medium. When Pseudomonas aeruginosa was cultured in a medium that had been treated with a metal affinity resin, the in vivo formation of the FpvA-Pvd complex and the recycling of Pvd on FpvA were nearly abolished. The accumulation of Pvd in the periplasm of Pseudomonas aeruginosa was also reduced in the treated growth medium, while the addition of 1 M AlCl 3 to the treated medium restored the effects of trace metals observed in standard growth medium. Using fluorescent resonance energy transfer and surface plasmon resonance techniques, the in vitro interactions between Pvd and detergent-solubilized FpvA were also shown to be metal dependent. We demonstrated that FpvA binds Pvd-Fe but not Pvd and that Pvd did not compete with Pvd-Fe for FpvA binding. In light of our finding that the Pvd-Al complex is transported across the outer membrane of Pseudomonas aeruginosa, a model for siderophore recognition based on a metal-induced conformation followed by redox selectivity for iron is discussed.The poor bioavailability of iron in aerobic environments, which is due to the low solubility of ferric hydroxide, has promoted the evolution of many iron-scavenging and storage molecules in organisms whose requirements for iron exceed the concentration of soluble free iron found under physiological conditions (ϳ10 Ϫ9 M). Mammalian pathogens encounter even lower levels of free iron (ϳ10 Ϫ18 M) due to iron sequestration by the host and have likewise developed mechanisms to efficiently compete for this essential nutrient (23). An indispensable iron acquisition mechanism in gram-negative bacteria involves the secretion of Fe(III)-chelating molecules called siderophores (13) and the expression of their cognate outer membrane transporters (OMTs). A large family of OMTs actively transport ferric siderophores across the outer membrane by coupling the transport to the proton gradient of the inner membrane via the TonB/ExbB/ExbD complex. The TonB-dependent OMTs include the receptors for a wide variety of siderophores as well as for other, non-iron-containing molecules, yet to date, they have all been found to have a conserved structure with a similar binding site for the transported molecule (30). However, one intriguing difference among the siderophore receptors was the reported ability of the pyoverdine (Pvd) receptor from Pseudomonas aeruginosa (FpvA) (26) and the ferric citrate receptor from Escherichia coli (FecA) (32) to bind their siderophores in the absence of Fe. More recently, iron-free siderophore binding was re...

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Interaction of cyclosporin A with an Fab fragment or cyclophilin Affinity measurements and time‐dependent changes in binding

Cited by 27 publications

References 17 publications

The 3D structure of a cyclosporin analogue in water is nearly identical to the cyclophilin‐bound cyclosporin conformation

The 3D structure of a cyclosporin analogue in water is nearly identical to the cyclophilin‐bound cyclosporin conformation

Binding Kinetics, Structure-Activity Relationship, and Biotransformation of the Complement Inhibitor Compstatin

The Metal Dependence of Pyoverdine Interactions with Its Outer Membrane Receptor FpvA

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