Subfamilies

Compounds having the 16,17 ketal, eg, budesonide, amcinonide, fluocinonide, halcinonide, triamcinolone acetonide, and flurandrenohde, also undergo metabohsm by routes that parahel that of cortisol metabohsm. Unsymmetrical acetals such as budesonide are also metabolized by routes not available to the more metabohcahy stable symmetrical 16a,17a-isopropyhdiene-dioxysubstituted compounds (desonide, flunisohde, and triamcinolone acetonide). Isozymes within the cytochrome P450 3A subfamily are thought to catalyze the metabohsm of budesonide, resulting in formation of 16a-hydroxyprednisolone and 6P-hydroxybudesonide (19,20) (Fig. 3) in addition to the more common metabohc steps (oxidation via reduction of A, etc). 

The world of zinc-containing DNA-binding proteins is by no means exhausted by these three subfamilies. Several other subfamilies are already known with different three-dimensional structures and different sequence patterns of cysteine and histidine residues that form the zinc ligands. Further subfamilies may well be discovered as the genomes of different species are sequenced whether or not any fundamentally new principles for DNA-protein recognition will be discovered amongst these new subfamilies remains to be seen. 

Figure 13.24 Six subfamilies of receptor tyrosine kinases involved in cell growth and differentiation. Only one or two members of each subfamily are indicated. Note that the tyrosine kinase domain is interrupted by a "kinase insert region" in some of the subfamilies. The functional significance of the cysteine-rich and immunoglobulin-like domains is unknown.

Similar transformations have not as yet been successfully applied to the tetracyclines bearing a hydroxy group at Cs, and no mutant culture has been reported that biosynthesizes a 6-deoxy-5-oxytetracycline. However, other means have been found to avoid 5a,6-dehydration in this subfamily. Treatment of 3 with N-... 

Inter [4+2]/intra [3+2] This typeof tandem reaction nsmg nitroalkenes hasbeen expbred most extensively Four subfamilies of tandem cycloaddiQon exist, which anse from the font different pomts of attachment of the dipolarophihc tether They are defined as fused, spiro, and bridged modes, as depicted m Scheme 8 37... 

The largest numbers of integrins are members of the (31 integrins, also known as the very late antigen (VLA) subfamily because of its late appearance after activation. There are at least seven receptors characterized from this subfamily, each with different ligand specificity. Among the most studied include the 04(31 and a5 31 receptors. The leukocyte integrin a4 31 is a cell adhesion receptor that is predominantly expressed on lymphocytes, monocytes and eosinophils. 

Another subfamily of ADP-iibosylating toxins modifies G-actin (at Argl77), thereby inhibiting actin polymerization. Members of this family are, for example, C. botulinum C2 toxin and Clostridium perfringens iota toxin. These toxins are binary in structure. They consist of an enzyme component and a separate binding component, which is structurally related to the binding component of anthrax toxin [3]. 

Important members of this toxin family are Clostridium difficile toxins A and B, which are implicated in antibiotics-associated diarrhea and pseudomembranous colitis. The large clostridial cytotoxins are single-chain toxins with molecular masses of 250-308 kDa. The enzyme domain is located at the N terminus. The toxins are taken up from an acidic endosomal compartment. They glucosylate RhoA at Thr37 also, Rac and Cdc42 are substrates. Other members of this toxin family such as Clostridium sordellii lethal toxin possess a different substrate specificity and modify Rac but not Rho. In addition, Ras subfamily proteins (e.g., Ras, Ral, and Rap) are modified. As for C3, they are widely used as tools to study Rho functions [2] [4]. 

Determining active site residues, and residues specific for subfamilies... 

This family contains more than 40 members subdivided into five subfamilies [4]. The NCS have been involved in phototransduction and regulation of neurotransmitter release. The NCS have two pairs of EF-hands and, unlike CaM and SI00 proteins, possess a consensus myristoylation sequence at the N-terminal responsible for the targeting of the NCS to the membrane. 

Cadherins are a superfamily of Ca2+-sensitive cell-cell adhesion molecules, which cause homophilic cell interactions. Cadherins can be divided into different subfamilies, namely, classical cadherins, desmosomal cadherins, protocadherins, and nonconventional cadherins (7TM cadherins, T-cadherin, FAT). Classical cadherins are often denoted by a prefix reflecting their principal expression domains e.g., E is epithelial, N is neuronal, and P is placental. However, this classification is not stringent, as for instance E-cadherin can also be found in certain neuronal tissues, and N-cadherin is also found in epithelial cells. Among the desmosomal cadherins, two subfamilies can be distinguished the desmocollins 1-3 and the desmogleins 1-4. 

Cytokeratins are members of the intermediate filament class of cytoskeletal proteins. Cytokeratins are a large protein family comprising two subfamilies of polypeptides, i.e. acidic (type I) and basic (type II) ones. Cytokeratin form tetramers, consisting of two type I and two type II polypeptides arranged in pairs of laterally aligned coiled coils. The distribution of the different type I and II cytokeratins in normal epithelia and in carcinomas is differentiation-related and can be used for cell typing and identification. 

Glucocorticoid Receptor GR GCR GRL Nuclear Receptor Subfamily 3, Group C, Member 1 (NR3C1) Glucocorticoid Receptor Type II Mineralocorticoid Receptor MR MCR MRL Nuclear Receptor Subfamily 3, Group C, Member 2 (NR3C2) Glucocorticoid Receptor Type I Aldosterone Receptor... 

Seven subfamilies of eukaryotic Kir channels, each sharing 60% amino acid identity between individual members within each subfamily and 40% identity between subfamilies, are known [1]. In addition, multiple prokaryotic Kir channels (Kirbacl.1-9) are now being identified in bacterial genomes. We will focus on the eukaryotic channels. 

All Kir channels are tetrameric proteins (see Fig. 3) of one-pore/two-transmembrane (1P/2TM) domain subunits which equally contribute to the formation of highly selective K+ channels. Most Kir channels can be assembled in functional homotetramers while some require heteromeric assembly (see Fig. 3). For example, functional GIRK channels underlying DCAch (Acetyl-choline-activated) current in atria are heteromultimers of two members ofKir3 subfamily Kir3.1 andKir3.4. 

Kv 3 -subunits are auxiliary subunits of Shaker-related Kv-channels, which belong to the Kvl subfamily of voltage-gated potassium channels. Kv(3 -subunits may function as chaperones in Kva -subunit assembly and may modulate the gating properties of Kv-channels. In particular, some Kv(3 -subunits may confer a rapid inactivation to otherwise non-inactivating Kv-channels. 

Three subclasses Bl, B2 and B3 can be distinguished on the basis of the sequences. Bl and B3 enzymes are optimally active with 2 Zn2+ions, while the B2 enzymes are inhibited by the second Zn2+. These B2 enzymes also exhibit a very narrow activity spectrum and only hydrolyse carbapenems. The 3D structures of representative members of each subfamily have been... 

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