Protein structure modulation

A constellation of genes code for PBPs of varying amino acid sequences and functionalities. PBPs occur as free-standing polypeptides and as protein fusions. This combinatorial system of structural modules results in a large increase in diversity. 

If cellular redox state, determined by the glutathione status of the heart, plays a role in the modulation of ion transporter activity in cardiac tissue, it is important to identify possible mechanisms by which these effects are mediated. Protein S-,thiolation is a process that was originally used to describe the formation of adducts of proteins with low molecular thiols such as glutathione (Miller etal., 1990). In view of the significant alterations of cardiac glutathione status (GSH and GSSG) and ion-transporter activity during oxidant stress, the process of S-thiolation may be responsible for modifications of protein structure and function. 

How does PARP-Fs role as a nucleosome-binding protein and modulator of chromatin structure, which is evident under normal physiological conditions, impact PARP-1-dependent DNA repair, cell death, and inflammatory response pathways, which occur under pathophysiological conditions A number of different scenarios are possible. For example, PARP-l s chromatin-dependent activities may be critical for its function as a DNA repair protein, since the repair of genomic DNA must occur in the context of chromatin. In addition, nucleosome-stimulated autoPARylation may play a role in depleting cellular NAD+ pools in response to cellular stresses. Furthermore, PARP-Fs chromatin-dependent activities may help to regulate the expression of immune and inflammatory response genes. These possibilities will need to be examined in the future. 

In addition to its influence on protein—protein interactions, phosphorylation also affects protein structure and activity. One case involves a protein termed dematin headpiece (DHP), an actin-binding protein found in a variety of tissues including heart, brain, skeletal muscle, kidney, and lung." DHP is known to interact with Ras-guanine nucleotide exchange factor (Ras-GRF2) and this interaction can modulate MARK pathways, which can link the cytoskeleton and signaling pathways." ... 

A series of carboxyl containing bioerodible polymeric materials, characterized by modulated functionality and hydrophobic/hydrophilic balance, was prepared both on a lab-scale and in the pilot plant. Procedures were setup as amenable for scaled-up productions. Those materials displayed a high versatility to combine with proteins in different proportion and to provide hybrid bioerodible matrices without any adverse effect on protein structure and activity. 

H.Y. Lee, K.H. Lee, H.M. Al-Hashimi, E.N.G. Marsh, Modulating protein structure with fluorous amino acids Increased stability and native-like structure conferred on a 4-helix bundle protein by hexafluoroleucine, J. Am. Chem. Soc. 128 (2006) 337-343. 

All types of nucleic acids interact with proteins. Chromosomal DNA forms stable nonspecific complexes with structural proteins that stabilize their tertiary structure it also forms transient complexes with enzymes and regulatory proteins that modulate DNA and RNA metabolism. The gross tertiary structure of DNA in E. coli and a typical eukaryotic chromosome is described in the next section. 

As mentioned above, the WW domain is another example of a protein-protein interaction module that binds proline-rich sequences (Kay et al., 2000). Dystrophin and utrophin WW domains interact predominantly with the extracellular matrix receptor dystroglycan, which contains a type 1 WW motif of consensus PPxY (reviewed in Ilsley et al., 2002 Winder, 2001). A structure of a WW domain from dystrophin was solved recently as part of a structure including the EF-hand region, and also with and without a bound /3-dystroglycan peptide (Huang et al., 2000). 

Yuan, X., Downing, A. K., Knott, V., and Handford, P. A. (1997). Solution structure of the transforming growth factor beta-binding protein-like module, a domain associated with matrix fibrils. EMBO J. 16, 6659-6666. 

Bischoff S, Leonhard S, Reymann N et al (1999) Spatial distribution of GABAb R1 receptor mRNA and binding sites in the rat brain. J Comp Neurol 412 1-16 Blein S, Ginham R, Uhrin D et al (2004) Structural analysis of the complement control protein (CCP) modules of GABAb receptor la. J Biol Chem 279 48292-306 Bockaert J, Pin J-P (1999) Molecular tinkering of G-protein-coupled receptors an evolutionary success. EMBO J 18 1723-9... 

Insight II Program with modules for homology modeling, protein structure analysis, pharmacophore/3D-QSAR modeling, MD www.accelrys.com/insight/Insight2.html... 

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