Avdonin P V, Panchenko M P, Tkachuk V A
Biokhimiia. 1980 Nov;45(11):1970-9.
The GTP analog, guanyl-5'-ilimidodiphosphate (Gpp(NH)p) activates rabbit heart adenylate cyclase with the lag period eliminated by isoproterenol. The Gpp(NH)p-isoproterenol-induced state of adenylate cyclase is very stable and is retained after removal of the effector excess and a 40-min incubation at 37 degrees. GTP and NaF decrease the activity of Gpp (NH)p-stimulated adenylate cyclase. This effect of GTP appears with the lag period, which is not affected by isoproterenol. GTP and Gpp(NH)p compete for the same binding site; it is assumed that GTP can remove Gpp(NH)p from the regulatory center of heart adenylate cyclase. The inhibiting effect of NaF on Gpp(NH)p-stimulated enzyme is reversible, has no lag period and is not accompanied by the Gpp(NH)p removal from the regulatory center of the enzyme. The data obtained suggest that the hormones control the activity of adenylate cyclase during GTP substitution for GDP, but do not change the rate of guanosine triphosphate dissociation from the nucleotide binding site of the enzyme. NaF does not probably affect the binding of guanylic nucleotides, but changes the type of interaction of the catalytic subunit of adenylate cyclase with the regulatory protein binding guanylic nucleotides.
GTP类似物鸟苷-5'-亚氨二磷酸（Gpp(NH)p）可激活兔心脏腺苷酸环化酶，而异丙肾上腺素可消除其延迟期。Gpp(NH)p-异丙肾上腺素诱导的腺苷酸环化酶状态非常稳定，在去除过量效应物并于37℃孵育40分钟后仍能保持。GTP和NaF可降低Gpp(NH)p刺激的腺苷酸环化酶的活性。GTP的这种作用会出现延迟期，而异丙肾上腺素对此无影响。GTP和Gpp(NH)p竞争同一结合位点；推测GTP可从心脏腺苷酸环化酶的调节中心去除Gpp(NH)p。NaF对Gpp(NH)p刺激的酶的抑制作用是可逆的，无延迟期，且不会伴随着Gpp(NH)p从酶的调节中心去除。所获得的数据表明，在GTP替代GDP的过程中，激素控制腺苷酸环化酶的活性，但不会改变三磷酸鸟苷从酶的核苷酸结合位点解离的速率。NaF可能不影响鸟苷酸的结合，但会改变腺苷酸环化酶催化亚基与结合鸟苷酸的调节蛋白的相互作用类型。
