GTP derived Cyclic Nucleotides
Cyclic Nucleotides Metabolism

Author: Gianpiero Pescarmona
Date: 11/10/2007

Description

cGMP synthesis

Guanylate Cyclase

Cyclic Diguanosine Monophosphate (c-di-GMP)
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Cyclic Diguanosine Monophosphate (c-di-GMP, cyclic diguanylate, cyclic-di-gmp) is a second messenger used in signal transduction in bacteria, important in studies of bacterial virulence, bacterial infectiousness, pathogenesis, vaccine adjuvants (potentially in MRSA vaccines), bacterial biofilm formation, bacterial cell-cell interactions, and bacterial cell adhesion. Biological activity regulated by c-di-GMP is mediated through binding to many different receptors.

c-di-GMP is important in studies of bacterial virulence, bacterial infectiousness, pathogenesis, vaccine adjuvants (potentially in MRSA vaccines), bacterial biofilm formation, bacterial cell-cell interactions, and bacterial cell adhesion. Biological activity regulated by c-di-GMP is mediated through binding to many different receptors.

From the laboratory of Roger A. Jones, PhD, Rutgers University.

Comments
2008-10-04T10:53:31 - alessia russo

Cyclic guanosine monophosphate(cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP, most notably by activating intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell surface.

cGMP-Wikipedia

cGMP synthesis is catalyzed by guanylate cyclase (GC), which converts GTP to cGMP. Membrane-bound GC is activated by peptide hormones such as the atrial natriuretic factor, while soluble GC is typically activated by nitric oxide to stimulate cGMP synthesis.

Guanylate cyclase is a lyase enzyme. In biochemistry, a lyase is an enzyme that catalyzes the breaking of various chemical bonds by means other than hydrolysis and oxidation, often forming a new double bond or a new ring structure. For example, an enzyme that catalyzed this reaction would be a lyase:

GTP → cGMP + PPi

Guanylate Cyclase-Wikipedia

There are membrane-bound or particulate (type 1) and soluble (type 2) forms of guanylyl cyclases.

Soluble and Particulate GC

Nitric oxide’s mechanism of activation of Soluble GC


Nature Reviews

Poulos T.L.,Soluble guanylate cyclase,Curr Opin Struct Biol,2006

Particulate Guanylate Cyclase

The activity of particulate cyclases appears to be regulated in a more complex way.

Particulate cyclases have been found in almost all tissues and cell types, however, their distribution is isoform specific. Seven different isoforms of the enzyme, in rat termed GC-A through GC-G.

Particulate guanylyl cyclases:multiple mechanism of activation,Kobiałka M.et al.,Acta Biochim Pol. 2000

PDE

Cyclic GMP may serve as a subtle switch between different signal transduction pathways.The nucleotide is

  • an activator of protein kinases (Lohman et al.,1997)
  • can activate or inhibit phosphodiesterases of cAMP (Beavo, 1995)
  • directly regulates the opening of cationic channels (Finn et al., 1996).
The intracellular level of the nucleotide is controlled by the activity of opposite enzymes: synthesizing guanylyl cyclases (GCs) and hydrolyzing phosphodiesterases (PDEs).

Phosphodiesterases-Wikipedia

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