[Structural and functional bases of the intermolecular interaction of calix[4]arene C-97 with myosin subfragment-1 of myometrium].
Calix[4]arene C-97 (code is shown) is the macrocyclic compound which has lipophilic intramolecular higly-structured cavity formed by four aromatic cycles, one of which on the upper rim is modified by methylene bisphosphonic group. It was shown that calix[4]arene C-97 (100 microM) efficiently inhibits ATPase activity of myosin subfragment-1 from pig myometrium, the inhibition coefficient I(0.5) being 83 +/- 7 microM. At the same time, this compound at 100 microM concentration significantly increases the effective hydrodynamic diameter of myosin subfragment-1, that may be indicative of intermolecular complexation between the calix[4]arene and myosin head. Computer simulation methods (docking, molecular dynamics, involving the Grid) have been used to clarify structural basis of the intermolecular interaction of calix[4]arene C-97 with myosin subfragment-1 of the myometrium; participation of hydrophobic, electrostatic and pi-pi (stacking) interactions between calix[4]arene C-97 and amino acid residues of myosin subfragment-1, some of them being located near the active site of the ATPase has been found out.
R D
RD
Labyntseva
A A
AA
Bevza
O V
OV
Bevza
S O
SO
Cherenok
V I
VI
Kal'chenko
S O
SO
Kosterin
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D000818:Animals; D047250:Calixarenes / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D020134:Catalytic Domain; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008958:Models, Molecular; D009215:Myometrium / Q000737:chemistry*; D015879:Myosin Subfragments / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D011485:Protein Binding; D055672:Static Electricity; D013552:Swine
D004791:Enzyme Inhibitors; D015879:Myosin Subfragments; D047250:Calixarenes; D000251:Adenosine Triphosphatases