Iterative schemes for bilinear operators; application to spin decoupling

Shaka, A.J.; Lee, C.J; Pines, Alexander

doi:10.1016/0022-2364(88)90178-3

Cited by 574 publications

(610 citation statements)

References 13 publications

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“…All spectra were processed using BRUKER TOPSPIN (version 3.2, Bruker Corporation, Billerica, MA, USA) and analysed using CCPNMR-ANALYSIS (version 2.1.5, University of Cambridge, Cambridge, UK). 1 H chemical shifts were referenced to 3-trimethylsilyl-1-propanesulfonic acid sodium sulfate (DSS), while 13 C and 15 N chemical shifts were referenced indirectly through their gyromagnetic ratios [21]. The chemical shift assignments are summarized in Figs S3 and S6 and accessible at the BioMag ResBank (BMRB) website (CP1, BMRB ID: 26676; CP2, BMRB ID: 26677).…”

Section: Nmr Spectroscopymentioning

confidence: 99%

Redox‐stable cyclic peptide inhibitors of the SPSB2–iNOS interaction

et al. 2016

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Edited by Barry HalliwellSPSB2 mediates the proteasomal degradation of iNOS. Inhibitors of SPSB2-iNOS interaction are expected to prolong iNOS lifetime and thereby enhance killing of persistent pathogens. Here, we describe the synthesis and characterization of two redox-stable cyclized peptides containing the DINNN motif required for SPSB2 binding. Both analogues bind with low nanomolar affinity to the iNOS binding site on SPSB, as determined by SPR and 19 F NMR, and efficiently displace full-length iNOS from binding to SPSB2 in macrophage cell lysates. These peptides provide a foundation for future development of redox-stable, potent ligands for SPSB proteins as a potential novel class of anti-infectives.Keywords: anti-infective; cyclic peptide; inducible nitric oxide synthase; redox-stable; SPRY domain of the SOCS-box protein 2 SPSB2 protein plays a key role in modulating the lifetime of iNOS in macrophages during infection [1]. It acts as a negative regulator that recruits an E3 ubiquitin ligase complex that polyubiquitinates iNOS and thereby mediates its proteasomal degradation [1]. SPSB2-deficient macrophages exhibit prolonged iNOS expression, NO production and ultimately enhanced killing of persistent pathogens such as Leishmania major parasites and Mycobacterium tuberculosis, suggesting that inhibitors of the SPSB2-iNOS interaction have potential as a new class of anti-infectives [1].Kuang et al. [1] showed that a linear peptide from the disordered N-terminal region of iNOS, KEEK-DINNNVKKT, bound to SPSB2 with a K D of 13 nM, and that the most important residues mediating this interaction were DINNN, in particular the first, third and fifth residues of this sequence motif. In addition, structural studies by X-ray crystallography revealed that the SPRY domain of SPSB2 binds to Asp184, Asn186 and Asn188 of the DINNN sequence of the VASA peptide, the same motif as in the N-terminal region of iNOS (where the corresponding residues are Asp23, Asn25Abbreviations SPSB2, SPRY domain of the SOCS-box protein 2; iNOS, inducible nitric oxide synthase; SPR, surface plasmon

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Section: Nmr Spectroscopymentioning

confidence: 99%

Redox‐stable cyclic peptide inhibitors of the SPSB2–iNOS interaction

et al. 2016

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“…For NOESY-HMQC experiments, a NOESY mixing time of 80 ms was used, with saturation of the water signal during mixing. In TOCSYtype experiments, Hartmann-Hahn coherence transfer was accomplished using the DIPSI-2 sequence for isotropic mixing (Shaka et al, 1988). A 7.5-kHz spin locking field was used with a 60-ms mixing time.…”

Section: Nmr Spectroscopymentioning

confidence: 99%

Redox‐dependent dynamics of putidaredoxin characterized by amide proton exchange

Lyons¹,

Ratnaswamy²,

Pochapsky³

1996

Protein Science

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Multidimensional NMR methods were used to obtain 'H-I'N correlations and "N resonance assignments for amide and side-chain nitrogens of oxidized and reduced putidaredoxin (Pdx), the Fe2S2 ferredoxin, which acts as the physiological reductant of cytochrome P-450,,, (CYPlOl). A model for the solution structure of oxidized Pdx has been determined recently using NMR methods (Pochapsky TC, Ye XM, Ratnaswamy G, Lyons TA, 1994, Biochemistry 33:6424-6432) and redox-dependent ' H NMR spectral features have been described (Pochapsky TC, Ratnaswamy G, Patera A, 1994, Biochemistry33:6433-6441). "N assignments were made with NOESY-('H/''N) HMQC and TOCSY-('H/''N) HSQC spectra obtained using samples of Pdx uniformly labeled with "N. Local dynamics in both oxidation states of Pdx were then characterized by comparison of residue-specific amide proton exchange rates, which were measured by a combination of saturation transfer and H 2 0 / D 2 0 exchange methods at pH 6.4 and 7.4 (uncorrected for isotope effects). In general, where exchange rates for a given site exhibit significant oxidation-state dependence, the oxidized protein exchanges more rapidly than the reduced protein. The largest dependence of exchange rate upon oxidation state is found for residues near the metal center and in a region of compact structure that includes the loop-turn Val 74-Ser 82 and the C-terminal residues (Pro 102-Trp 106). The significance of these findings is discussed in light of the considerable dependence of the binding interaction between Pdx and CYPlOl upon the oxidation state of Pdx.

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“…A NOESY-HSQC spectrum was acquired at 750 MHz and 160 ms for comparison. Finally, a 40-ms TOCSY-HSQC spectrum was acquired at 500 MHz using the same basic pulse sequence and DIPSI-2 mixing (Shaka et al, 1988) to facilitate "N resonance assignments. All spectra were processed using 3-Hz exponential line-broadening in the acquired dimension and squared-cosine bell window functions in the nonacquired dimensions.…”

Section: Cross-reluxulion Experimentsmentioning

confidence: 99%

Comparison of the accuracy of protein solution structures derived from conventional and network‐edited NOESY data

et al. 1995

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Network-editing experiments are variants of the basic NOESY experiment that allow more accurate direct measurement of interproton distances in macromolecules by defeating specific spin-diffusion pathways. Two network-editing approaches, block-decoupled NOESY and complementary-block-decoupled-NOESY, were applied as three-dimensional, heteronuclear-edited experiments to distance measurement in a small protein, turkey ovomucoid third domain (OMTKY3). Two-hundred and twelve of the original 655 distance constraints observed in this molecule (Krezel AM et al., 1994, JMol Biol242:203-214) were improved by their replacement by distances derived from networkedited spectra, and distance geometryhimulated annealing solution structure calculations were performed from both the unimproved and improved distance sets. The resulting two families of structures were found to differ significantly, the most important differences being the hinge angle of a 0-turn and an expansion of the sampled conformation space in the region of the reactive-site loop. The structures calculated from network-editing data are interpreted as a more accurate model of the solution conformation of OMTKY3.Keywords: BD-NOESY-HSQC; CBD-NOESY-HSQC; cross relaxation; network editing; "N NMR assignments; NOESY; nuclear magnetic resonance; protein structure; spin diffusionThe accuracy and reliability of structural models derived by NMR is a key issue in the methodology of structure determination. In the context of a drug-development study, for example, a relatively minor structural distortion can lead to a tremendous amount of wasted effort on the part of synthetic chemists. NMR data directly determine only short-range constraints, and those with relatively low precision, but yield those constraints in great abundance such that converged and apparently highly precise structures are obtained. Therefore, the extent to which the accuracy and precision of distance measurements will affect the quality of derived structural models has been a source of controversy for some time.Two different approaches can be taken in improving the accuracy of distance measurements derived from NMR data. One approach makes use of a model structure in the analysis of the full relaxation matrix (Boelens et al

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Iterative schemes for bilinear operators; application to spin decoupling

Cited by 574 publications

References 13 publications

Redox‐stable cyclic peptide inhibitors of the SPSB2–iNOS interaction

Redox‐stable cyclic peptide inhibitors of the SPSB2–iNOS interaction

Redox‐dependent dynamics of putidaredoxin characterized by amide proton exchange

Comparison of the accuracy of protein solution structures derived from conventional and network‐edited NOESY data

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