ChemInform Abstract: REVERSIBLE BINDING OF ACETYLENE BY OXOBIS(DIETHYLDITHIOCARBAMATE)MOLYBDENUM

1978 ◽  
Vol 9 (24) ◽  
Author(s):  
E. A. MAATTA ◽  
R. A. D. WENTWORTH ◽  
W. E. NEWTON ◽  
J. W MCDONALD ◽  
G. D. WATT
Keyword(s):  
Reversible Binding

A STUDY OF REVERSIBLE BINDING OF MOLECULAR OXYGEN TO COBALT(II) OCTAETHYLPORPHYRIN BY57Co MÖSSBAUER EMISSION SPECTROSCOPY

1978 ◽  
Vol 7 (4) ◽  
pp. 353-356 ◽  
Author(s):  
Hiroshi Sakai ◽  
Yutaka Maeda ◽  
Hisanobu Ogoshi ◽  
Hiroshi Sugimoto ◽  
Zen-ichi Yoshida
Keyword(s):  
Molecular Oxygen ◽  
Emission Spectroscopy ◽  
Reversible Binding

Reversible binding of 5- and 8-methoxypsoralen to human serum proteins (albumin) and to epidermis in vitro

1979 ◽  
Vol 101 (6) ◽  
pp. 669-677 ◽  
Author(s):  
M. ARTUC ◽  
G. STUETTGEN ◽  
W. SCHALLA ◽  
H. SCHAEFER ◽  
J. GAZITH
Keyword(s):  
Human Serum ◽  
Serum Proteins ◽  
Reversible Binding ◽  
Human Serum Proteins

scholarly journals Crystal structure of human carbonic anhydrase II at 1.95 Å resolution in complex with 667-coumate, a novel anti-cancer agent

2005 ◽  
Vol 385 (3) ◽  
pp. 715-720 ◽  
Author(s):  
Matthew D. LLOYD ◽  
Richard L. PEDERICK ◽  
Ramanathan NATESH ◽  
L. W. Lawrence WOO ◽  
Atul PUROHIT ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Phase 1 ◽  
Structural Basis ◽  
Pharmacokinetic Studies ◽  
Reversible Binding ◽  
X Ray Crystallography ◽  
Hydrophobic Binding ◽  
Cancer Agent

CA (carbonic anhydrase) catalyses the reversible hydration of carbon dioxide into bicarbonate, and at least 14 isoforms have been identified in vertebrates. The role of CA type II in maintaining the fluid and pH balance has made it an attractive drug target for the treatment of glaucoma and cancer. 667-Coumate is a potent inhibitor of the novel oncology target steroid sulphatase and is currently in Phase 1 clinical trials for hormone-dependent breast cancer. It also inhibits CA II in vitro. In the present study, CA II was crystallized with 667-coumate and the structure was determined by X-ray crystallography at 1.95 Å (1 Å=0.1 nm) resolution. The structure reported here is the first for an inhibitor based on a coumarin ring and shows ligation of the sulphamate group to the active-site zinc at 2.15 Å through a nitrogen anion. The first two rings of the coumarin moiety are bound within the hydrophobic binding site of CA II. Important residues contributing to binding include Val-121, Phe-131, Val-135, Leu-141, Leu-198 and Pro-202. The third seven-membered ring is more mobile and is located in the channel leading to the surface of the enzyme. Pharmacokinetic studies show enhanced stability of 667-coumate in vivo and this has been ascribed to binding of CA II in erythrocytes. This result provides a structural basis for the stabilization and long half-life of 667-coumate in blood compared with its rapid disappearance in plasma, and suggests that reversible binding of inhibitors to CA may be a general method of delivering this type of labile drug.

scholarly journals Signaling pathways have an inherent need for noise to acquire information

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Eugenio Azpeitia ◽  
Eugenio P. Balanzario ◽  
Andreas Wagner
Keyword(s):  
Signaling Pathways ◽  
Information Acquisition ◽  
Cellular Level ◽  
Kinetic Properties ◽  
Positive Role ◽  
Binding Interactions ◽  
Reversible Binding ◽  
Wide Range ◽  
The One ◽  
Parameter Values

Abstract Background All living systems acquire information about their environment. At the cellular level, they do so through signaling pathways. Such pathways rely on reversible binding interactions between molecules that detect and transmit the presence of an extracellular cue or signal to the cell’s interior. These interactions are inherently stochastic and thus noisy. On the one hand, noise can cause a signaling pathway to produce the same response for different stimuli, which reduces the amount of information a pathway acquires. On the other hand, in processes such as stochastic resonance, noise can improve the detection of weak stimuli and thus the acquisition of information. It is not clear whether the kinetic parameters that determine a pathway’s operation cause noise to reduce or increase the acquisition of information. Results We analyze how the kinetic properties of the reversible binding interactions used by signaling pathways affect the relationship between noise, the response to a signal, and information acquisition. Our results show that, under a wide range of biologically sensible parameter values, a noisy dynamic of reversible binding interactions is necessary to produce distinct responses to different stimuli. As a consequence, noise is indispensable for the acquisition of information in signaling pathways. Conclusions Our observations go beyond previous work by showing that noise plays a positive role in signaling pathways, demonstrating that noise is essential when such pathways acquire information.

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