Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ion entry into neurons occurs either through receptor-operated channels (ROC) or voltage-operated channels (VOC). The function of ROC depends crucially on the action of agonists, antagonists or compounds modulating particular types of receptors (GABA A, NMDA, Ach N receptors). The function of VOC is closely connected with the activity of protein kinases and the processes of phosphorylation of membrane proteins (K+, Na+, Ca2+ channels). Gamma aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the vertebrate brain. The GABA A receptor is a oligomeric complex of multiple binding sites and chloride channel. This complex contains recognition sites for GABA, anxiolytics such as benzodiazepine, anxiogenic--beta-carboline, and convulsant such as picrotoxin. Chloride ion channel plays a crucial role in anxiogenic, anxiolytic and convulsant activities. Glutamic acid is the main endogenous neurotransmitter for N-methyl-D-aspartate (NMDA)-type excitatory amino acid receptor. NMDA receptors connected with Ca2+ channel, have multiple modulatory sites which are affected by a wide range of compounds. There are NMDA and competitive NMDA antagonists site, the glycine site, the phencyclidine (PCP) site and the binding site of Mg2+ ions in this receptor complex. Calcium entry through NMDA receptors may be important in the etiology of many psychiatric disorders. VOC mediate rapid, voltage-gated changes in ion permeability during action potentials in neurons. Electrophysiological studies indicate the existence of three types of VOC (K+, Na+, Ca2+ channels). In number of neurons various subtypes of Ca2+ channels (P, T, N and L-type) occur together. Among them, the L-type calcium channel has been first described and most thoroughly studied. The L-type calcium channel is localized on nerve terminals in the pre and postsynaptic parts, as well as on cell bodies and may be involved in the mechanism of action of psychotropic drugs. Chronic treatment with various psychotropic drugs changes the density of voltage-dependent Ca2+ channels in the central nervous system. Thus calcium entry through both VOC and ROC may be important in the etiology of many psychiatric disorders.
Pol J Pharmacol
PMID:Receptor and voltage-operated ion channels in the central nervous system. 871 58

The catalytic reaction mediated by DNA polymerases is known to require two Mg(II) ions, one associated with dNTP binding and the other involved in metal ion catalysis of the chemical step. Here we report a functional intermediate structure of a DNA polymerase with only one metal ion bound, the DNA polymerase beta-DNA template-primer-chromium(III).2'-deoxythymidine 5'-beta,gamma-methylenetriphosphate [Cr(III).dTMPPCP] complex, at 2.6 A resolution. The complex is distinct from the structures of other polymerase-DNA-ddNTP complexes in that the 3'-terminus of the primer has a free hydroxyl group. Hence, this structure represents a fully functional intermediate state. Support for this contention is provided by the observation of turnover in biochemical assays of crystallized protein as well as from the determination that soaking Pol beta crystals with Mn(II) ions leads to formation of the product complex, Pol beta-DNA-Cr(III).PCP, whose structure is also reported. An important feature of both structures is that the fingers subdomain is closed, similar to structures of other ternary complexes in which both metal ion sites are occupied. These results suggest that closing of the fingers subdomain is induced specifically by binding of the metal-dNTP complex prior to binding of the catalytic Mg(2+) ion. This has led us to reevaluate our previous evidence regarding the existence of a rate-limiting conformational change in Pol beta's reaction pathway. The results of stopped-flow studies suggest that there is no detectable rate-limiting conformational change step.
 ...
PMID:Insight into the catalytic mechanism of DNA polymerase beta: structures of intermediate complexes. 1133 Sep 99