Regulatory domains

The two domains of the kinase in the inactive state are held in a closed conformation by assembly of the regulatory domains... 

PDE Family Genes Probable splice variants Regulatory domains/role Phosphorylation Substrate (s) Commonly used inhibitors... 

Wu, B., Kingston, R.E., Morimoto, R.I. (1986). Human hsp70 promoter contains at least two distinct regulatory domains. Proc. Natl. Acad. Sci. USA 83,629-633. 

PPD Purified protein derivative PPME Polymeric polysaccharide rich in mannose-6-phosphate moieties PRA Percentage reactive activity PRD, PRDII Positive regulatory domain, -II PR3 Proteinase-3 PRBC Parasitized red blood cell proET-1 Proendothelin-1 PRL Prolactin PRP Platelet-rich plasma PS Phosphatidylserine P-selectin Platelet selectin formerly known as platelet adctivation-dependent granule external membrane protein (PADGEM), granule membrane protein of MW 140 kD (GMP-140)... 

In addition to the possible C2,C2 -substituent interactions with a hydrophobic pocket in the regulatory domain site, the much higher affinity of calphostin A (Chart 7.1 4a, R1 = R2 = COPh, IC50 = 0.25 pM) compared to calphostin D (4d, R1 = R2 = H, IC50 = 6.4 pM) also points to interaction of the C7,C7 -portion with the binding site [51]. The C2,C2 - and C7,C7 -analogs would be invaluable in understanding the relative importance of each of these interactions. To determine... 

Ca2+ [66], making calcium monitoring a vital tool for cellular biologists. For example, calmodulin-dependent protein phosphatase, calcineurin can be monitored using a probe based on the regulatory domain of the nuclear factor of activated T cells [69], This approach can be taken further to monitor multiple calcium-dependent events in real time [70],... 

FIGURE 21-6 Schematic illustration of the overall structure and regulatory sites of eleven different phosphodiesterase subtypes. The catalytic domain of the phosphodiesterases are relatively conserved, and the preferred substrate(s) for each type is shown. The regulatory domains are more variable and contain the sites for binding of Ca2+/calmodulin (CaM) and cGMP, as well as GAF and PAS domains. The regulatory domains also contain sites of phosphorylation by cAMP-dependent protein kinase (PKA). 

Nonreceptor protein tyrosine kinases contain a catalytic domain, as well as various regulatory domains important for proper functioning of the enzyme 416... 

Nonreceptor protein tyrosine kinases contain a catalytic domain, as well as various regulatory domains important for proper functioning of the enzyme. NRPTKs are found in the inner leaflet of the plasma membrane, cytosol, endosomal membranes and nucleus. These include the Src, Jak, Abl, Tec, Ack, Csk, Fak, Fes, Frk and Syk subfamilies (Fig. 24-3). Since a great deal is known about the structure and regulation of the Src family tyrosine kinase, we will use it to illustrate the principles in NRPTK signaling unique features in other subfamilies will be indicated... 

FIGURE 24-10 Schematic structures of nonreceptor protein tyrosine phosphatases (NRPTPs) and receptor protein tyrosine phosphatases (RPTPs). NRPTPs contain a catalytic domain and various regulatory domains. RPTPs are composed of an extracellular domain, a transmembrane domain and an intracellular domain with one or two catalytic domains. Like receptor protein tyrosine kinases, the structural features of the extracellular domains divide the RPTPs into different families. (With permission from reference [12]). 

There are three types of selectins responsible for the attachment of leukocytes to the endothelium, as shown in Table 3.1. Selectins possess three types of domains a C-type lectin domain, an epidermal growth-factor-like domain and between two and nine regulatory domains. 

Fig. 2. An example of a complex multidomain protein that includes both domain concatenation and intercalation. (A) See color insert. RASMOL view of phosphotransferase pyruvate kinase (pdb entry lpkn) colored to show the three identifiable domains. Blue is the j3 barrel regulatory domain, orange is an eightfold a/fi barrel, the catalytic substrate binding domain, and green is a central /3, a/(B nucleotide binding domain. Not displayed is the leader subsequence composed of a random coil and short helix. (B) Linear order along the sequence of these components.

An in-depth study of DNA repair systems (Aravind et al., 1999a) has concluded that few, if any, repair proteins occur with identical collinear domain arrangements in all three kingdoms of life. Approximately 10 enzyme families of adenosine triphosphatases (ATPases), photolyases, helicases, and nucleases were identified that are all likely to have been present in the cenancestor. These enzymatic domains are accompanied in DNA repair proteins by numerous regulatory domains. This indicates that the domain architectures of these proteins are labile, with incremental addition and/or subtraction of domains to conserved cores to be a common phenomenon except in the most closely related species. 

By contrast few regulatory domains that function in eukaryotic signaling are detectable in prokaryotes (Ponting et al., 1999b). Of the 185 domain/motif families studied, only nine occur in all three kingdoms of life. Of these, several are likely to have been disseminated by horizontal... 

Aspartate transcarbamylase regulatory domains 1 and 2 Streptomyces subtilisin inhibitor Glutathione reductase domain 3 Thermolysin domain 1... 

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