X-ray and high-resolution 1H and 13C NMR of smooth muscle relaxant sesquiterpene lactones

2008 ◽  
Vol 86 (12) ◽  
pp. 1077-1084 ◽  
Author(s):  
Marie-Rose Van Calsteren ◽  
Christopher K Jankowski ◽  
Ricardo Reyes-Chilpa ◽  
Manuel Jiménez-Estrada ◽  
Maria G Campos ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
High Resolution ◽  
Muscle Relaxant ◽  
Sesquiterpene Lactones ◽  
Test Results ◽  
1H And 13C Nmr ◽  
X Ray ◽  
Nmr Data ◽  
High Resolution Nmr ◽  
Smooth Muscle Relaxant

The structure and stereochemistry of four sesquiterpene lactones, budlein A (1), zaluzanin A (2), and glaucolides D (3a) and E (3b), isolated from Mexican Asteraceae species, for which only partial NMR data could be found in the literature, were determined. A combination of 1D and 2D high-resolution NMR experiments, such as DEPT, COSY, NOESY, ROESY, HMQC, HSQC, and HMBC, were used to completely assign the 1H and 13C spectra. The crystal structures of zaluzanin A (2) and glaucolide E (3b) were also determined. Glaucolides D and E have been previously reported to relax KCl-induced contraction in rat uterine smooth muscle; therefore, the effects of zaluzanin A and budlein A were examined in the same model. It was found that both compounds can relax contraction induced by KCl, but only zaluzanin A induced relaxation when contraction was induced with oxytocin. The preliminary biological test results according to these profiles are reported in this paper.Key words: NMR data, X-ray data, sesquiterpene lactones, Mexican Asteraceae, smooth muscle relaxant.

scholarly journals High-resolution NMR studies of structure and dynamics of human ERp27 indicate extensive interdomain flexibility

2013 ◽  
Vol 450 (2) ◽  
pp. 321-332 ◽  
Author(s):  
Nader T. Amin ◽  
A. Katrine Wallis ◽  
Stephen A. Wells ◽  
Michelle L. Rowe ◽  
Richard A. Williamson ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
High Resolution ◽  
Nmr Relaxation ◽  
Full Length ◽  
15N Nmr ◽  
Nmr Studies ◽  
Average Order ◽  
X Ray ◽  
Nmr Data ◽  
High Resolution Nmr

ERp27 (endoplasmic reticulum protein 27.7 kDa) is a homologue of PDI (protein disulfide-isomerase) localized to the endoplasmic reticulum. ERp27 is predicted to consist of two thioredoxin-fold domains homologous with the non-catalytic b and b′ domains of PDI. The structure in solution of the N-terminal b-like domain of ERp27 was solved using high-resolution NMR data. The structure confirms that it has the thioredoxin fold and that ERp27 is a member of the PDI family. 15N-NMR relaxation data were obtained and ModelFree analysis highlighted limited exchange contributions and slow internal motions, and indicated that the domain has an average order parameter S2 of 0.79. Comparison of the single-domain structure determined in the present study with the equivalent domain within full-length ERp27, determined independently by X-ray diffraction, indicated very close agreement. The domain interface inferred from NMR data in solution was much more extensive than that observed in the X-ray structure, suggesting that the domains flex independently and that crystallization selects one specific interdomain orientation. This led us to apply a new rapid method to simulate the flexibility of the full-length protein, establishing that the domains show considerable freedom to flex (tilt and twist) about the interdomain linker, consistent with the NMR data.

Role of extracellular calcium and calmodulin in prolactin secretion induced by hyposmolarity, thyrotropin-releasing hormone, and high K+ in GH4C1 cells

1990 ◽  
Vol 123 (2) ◽  
pp. 218-224 ◽  
Author(s):  
Xiangbing Wang ◽  
Noriyuki Sato ◽  
Monte A. Greer ◽  
Susan E. Greer ◽  
Staci McAdams
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxant ◽  
Prolactin Secretion ◽  
Thyrotropin Releasing Hormone ◽  
Dependent Manner ◽  
Cell Toxicity ◽  
High K ◽  
Dose Dependent ◽  
Smooth Muscle Relaxant

Abstract. The mechanism by which 30% medium hyposmolarity induces PRL secretion by GH4C1 cells was compared with that induced by 100 nmol/l TRH or 30 mmol/l K+. Removing medium Ca2+, blocking Ca2+ channels with 50 μmol/l verapamil, or inhibiting calmodulin activation with 20 μmol/l trifluoperazine, 10 μmol/l chlorpromazine or 10 μmol/l pimozide almost completely blocked hyposmolarity-induced secretion. The smooth muscle relaxant, W-7, which is believed relatively specific in inhibiting the Ca2+-calmodulin interaction, depressed hyposmolarity-induced PRL secretion in a dose-dependent manner (r = −0.991, p<0.01 ). The above drugs also blocked or decreased high K+-induced secretion, but had much less effect on TRH-induced secretion. Secretion induced by TRH, hyposmolarity, or high K+ was optimal at pH 7.3-7.65 and was significantly depressed at pH 6.0 or 8.0, indicating that release of hormone induced by all 3 stimuli is due to an active cell process requiring a physiologic extracellular pH and is not produced by nonspecific cell toxicity. The data suggest hyposmolarity and high K+ may share some similarities in their mechanism of stimulating secretion, which is different from that of TRH.

Modulation of vascular tone by neutrophils: dependence on endothelial integrity

1989 ◽  
Vol 257 (4) ◽  
pp. H1315-H1320
Author(s):  
J. L. Mehta ◽  
D. L. Lawson ◽  
W. W. Nichols ◽  
P. Mehta
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Relaxant ◽  
Muscle Tone ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Smooth Muscle Tone ◽  
High Concentrations ◽  
Vascular Smooth Muscle Tone ◽  
Smooth Muscle Relaxant

To determine the influence of polymorphonuclear leukocytes (PMNLs) on vascular smooth muscle tone, isolated human PMNLs (10(4)–10(7) cells/ml) were suspended in a tissue bath with precontracted rat aortic rings with or without endothelium. PMNLs in low concentrations (10(4) and 10(5) cells/ml) caused a mild contraction, and in higher concentrations (10(6) and 10(7) cells/ml) caused a modest relaxation of aortic rings with intact endothelium. In contrast, PMNLs caused a potent concentration-dependent relaxation of deendothelialized rings (P less than 0.01 compared with rings with intact endothelium). The PMNL-induced vascular smooth muscle relaxation was abolished by both hemoglobin and methylene blue and potentiated by both superoxide dismutase and captopril. Although suspension of PMNLs caused release of eicosanoids, thromboxane A2 and prostacyclin, from rings with intact endothelium, neither indomethacin nor the TxA2-endoperoxide receptor antagonist SQ 29548 modified the effects of PMNLs on vascular smooth muscle tone. These observations suggest that unstimulated PMNLs generate a smooth muscle relaxant, which has biological characteristics similar to the endothelium-derived relaxing factor. Since the activity of this PMNL-derived smooth muscle relaxant is more pronounced in deendothelialized vascular segments, it appears that endothelium provides a barrier against vasorelaxation by high concentrations of PMNLs.

ChemInform Abstract: X-Ray Diffraction and High Resolution NMR Analysis of Methyl D-Glucopyranuronate Derivatives.

ChemInform ◽  
2001 ◽  
Vol 32 (6) ◽  
pp. no-no
Author(s):  
Anna Trynda ◽  
Janusz Madaj ◽  
Antoni Konitz ◽  
Andrzej Wisniewski
Keyword(s):  
High Resolution ◽  
Nmr Analysis ◽  
X Ray Diffraction ◽  
X Ray ◽  
High Resolution Nmr

Difference in Conformation of Virginiamycin M1 in Chloroform and Bound Form in the 50S Ribosome or Streptogramin Acetyltransferase

2004 ◽  
Vol 57 (5) ◽  
pp. 415 ◽  
Author(s):  
Jason Dang ◽  
B. Mikael Bergdahl ◽  
Frances Separovic ◽  
Robert T. C. Brownlee ◽  
Robert P. Metzger
Keyword(s):  
Crystal Structure ◽  
High Resolution ◽  
Active Site ◽  
Major Change ◽  
X Ray ◽  
Binding Process ◽  
High Resolution Nmr ◽  
Virginiamycin M1

The conformation of virginiamycin M1 (VM1) in chloroform, determined by high-resolution NMR experiments, differs significantly from that of the X-ray crystal structure of VM1 bound to the 50S ribosome and to the active site of a streptogramin acetyltransferase enzyme. This implies that the binding process to these entities causes a major change in VM1 conformation.

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