C subfamily

C subfamily of type 1 extradiol dioxygenases (Mars et al. 1999). The alternative extradiol fission of 3-chlorocatechol may take place between the 1 and 6 positions (distal fission), and this has been shown for the 2,3-dihydroxybiphenyl 1,2-dioxygenase from the naphthalene sulfonate degrading Sphingomonas sp. strain BN6 (Riegert et al. 1998). 

Based on the presence or absence of conserved cysteine residues within their primary sequence, the chemokine superfamily can be separated into four distinct subfamilies called the C-X-C (or a), the C-C (or (3), the C, or the C-X-X-X-C subfamilies (1-2). Chemokines share many other similarities including their high basic nature as well as their ability to bind heparin through heparinbinding domains. These molecules exhibit sequence identity at the amino acid level between 24 and 80%. Historically, the chemokine subfamilies... 

Fig. 11. Evolution of DNA polymerases. Upper panel distribution of DNA polymerases from A, B and C subfamilies between eubacteria, archaebacteria and eukaryotes. Lower panel alignments of regions 1 and 2a of E. coli DNA polymerase 11 (EcoPol II), Pyrococcus Juriosus (Pfii), Sulfolobus solfataricus (Sso), and human DNA polymerase-a (a-Hum). (Adapted from refs. [114,135-138].)...

We will first discuss the C subfamily of chemokines since it has only one member. Although the C subgroup just has one cysteine bond, it is functional. Lymphotactin is the name for the only characterized C chemokine (Kelner et al., 1994). Alignment of the amino acid sequence shows that this chemokine is missing one of the two N-terminal cysteines as well as the corresponding third cysteine. Although it does not have all the conserved cysteines, it does have chemotactic activity, indicating that the conserved amino acid substitutions in lymphotactin are able to maintain the functional conformation (Table 1). The lymphotactin receptor has recently been characterized and named XCRl (Yoshida et al., 1998). 

The first members of the C subfamily to be discovered displayed an inhibitory effect on adenylyl cyclase, hence the name Gi for inhibitory G proteins. Further members of the C subfamily have phospholipase C as the corresponding effector molecule. Signal transmission via phospholipase C flows into the inositol triphosphate and diacylgly-cerol pathways (see Chapter 6). 

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]. 

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... 

Harteneck C., Plant T.D. and Schultz G. (2000). From worm to man three subfamilies of TRP channels. Trends Neurosci 23, 159-166. 

Candia, A. F., Hu, J Crosby, J Lalley, R A., Noclen, D Nadeau, J., and Wright, C. V. E (1992). Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. Development 116 1123-1136. 

Falcone, F., Tetteh, K.K.A., Hunt, P., Blaxter, M.L., Loukas, A.C. and Maizels, R.M. (2000) The new subfamily of cathepsin Z-like protease genes includes Tc-cpz-1, a cysteine protease gene expressed in Toxocara canis adults and infective larvae. Experimental Parasitology 94, 201-203. 

Belinsky MG, Bain LJ, Balsara BB, Testa JR, Kruh GD. Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins. J Natl Cancer Inst 1998 90(22)7735-1741. 

Other electrophilic substitution reactions on aromatic and heteroaromatic systems are summarized in Scheme 6.143. Friedel-Crafts alkylation of N,N-dimethyl-aniline with squaric acid dichloride was accomplished by heating the two components in dichloromethane at 120 °C in the absence of a Lewis acid catalyst to provide a 23% yield of the 2-aryl-l-chlorocydobut-l-ene-3,4-dione product (Scheme 6.143 a) [281]. Hydrolysis of the monochloride provided a 2-aryl-l-hydroxycyclobut-l-ene-3,4-dione, an inhibitor of protein tyrosine phosphatases [281], Formylation of 4-chloro-3-nitrophenol with hexamethylenetetramine and trifluoroacetic acid (TFA) at 115 °C for 5 h furnished the corresponding benzaldehyde in 43% yield, which was further manipulated into a benzofuran derivative (Scheme 6.143b) [282]. 4-Chloro-5-bromo-pyrazolopyrimidine is an important intermediate in the synthesis of pyrazolopyrimi-dine derivatives showing activity against multiple kinase subfamilies (see also Scheme 6.20) and can be rapidly prepared from 4-chloropyrazolopyrimidine and N-bromosuccinimide (NBS) by microwave irradiation in acetonitrile (Scheme... 

Finally, a new area of research has concentrated on monocyte chemotactic protein-1 (MCP-1), a 76-amino acid peptide that is one of the best-studied members of the C-C chemokine subfamily. Recent human and animal studies indicate that the recruitment of macrophages to the arterial lesion is predom-... 

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