Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Size exclusion chromatographic analyses showed that Ca(2+)-free VILIP-1 contained both monomeric and dimeric forms, while no appreciable dimerization was noted with Ca(2+)-free VILIP-3. Swapping of EF-hands 3 and 4 of VILIP-1 with those of VILIP-3 caused the inability of the resulting chimeric protein to form dimeric protein. Nonreducing SDS-PAGE analyses revealed that most of the dimeric VILIP-1 was noncovalently bound together. Reduced glutathione (GSH)/oxidized glutathione (GSSG) treatment notably enhanced the formation of disulfide-linked VILIP-1 dimer, while Ca(2+) and Mg(2+) enhanced disulfide dimerization of VILIP-1 marginally in the presence of thiol compounds. Cys-187 at the C-terminus of VILIP-1 contributed greatly to form S-S-crosslinked dimer as revealed by mutagenesis studies. The ability of GSH/GSSG-treated VILIP-1 to activate guanylyl cyclase B was reduced by substituting Cys-187 with Ala. Together with disulfide dimer of VILIP-1 detected in rat brain extracts, our data may imply the functional contribution of disulfide dimer to the interaction of VILIP-1 with its physiological target(s).
 ...
PMID:Regulatory elements and functional implication for the formation of dimeric visinin-like protein-1. 1906 2

The neuronal calcium sensor proteins Visinin-like Proteins 1 (VILIP-1) and 3 (VILIP-3) are effectors of guanylyl cyclase and acetyl choline receptors, and transduce calcium signals in the brain. The "calcium-myristoyl" switch, which involves a post-translationally added myristoyl moiety and calcium binding, is thought to regulate their membrane binding capacity and therefore, play a critical role in their mechanism of action. In the present study, we investigated the effect of membrane composition and solvent conditions on the membrane binding mechanisms of both VILIPs using lipid monolayers at the air/buffer interface. Results based on comparison of the adsorption kinetics of the myristoylated and non-myristoylated proteins confirm the pivotal role of calcium and the exposed myristol moiety for sustaining the membrane-bound state of both VILIPs. However, we also observed binding of both VILIP proteins in the absence of calcium and/or myristoyl conjugation. We propose a two-stage membrane binding mechanism for VILIP-1 and VILIP-3 whereby the proteins are initially attracted to the membrane surface by electrostatic interactions and possibly by specific interactions with highly negatively charged lipids head groups. The extrusion of the conjugated myristoyl group, and the subsequent anchoring in the membrane constitutes the second stage of the binding mechanism, and ensures the sustained membrane-bound form of these proteins.
...
PMID:Comparison of VILIP-1 and VILIP-3 binding to phospholipid monolayers. 2469 24