Conserved domain

Lipid phosphate phosphohydrolases (LPPs), formerly called type 2 phosphatidate phosphohydrolases (PAP-2), catalyse the dephosphorylation of bioactive phospholipids (phosphatidic acid, ceramide-1-phosphate) and lysophospholipids (lysophosphatidic acid, sphingosine-1-phosphate). The substrate selectivity of individual LPPs is broad in contrast to the related sphingosine-1-phosphate phosphatase. LPPs are characterized by a lack of requirement for Mg2+ and insensitivity to N-ethylmaleimide. Three subtypes (LPP-1, LPP-2, LPP-3) have been identified in mammals. These enzymes have six putative transmembrane domains and three highly conserved domains that are characteristic of a phosphatase superfamily. Whether LPPs cleave extracellular mediators or rather have an influence on intracellular lipid phosphate concentrations is still a matter of debate. 

The Rel homology domain (RHD) is an evolutionarily conserved domain found in some eukaryotic transcription factors, including NF-kB, the nuclear factors of activated T-cells (NFATs) and the drosophila proteins Dif and Relish. Some of these transcription factors form... 

The method can be used in combination with a multiple domain dissection procedure (Adams, et al., 1996) to construct a near full-length domain profile when the common domain is masked by the presence of other more conserved domains. 

MACPF Conserved domain in membrane attack complex proteins and perforin E(MP)B 0(0) 0(0) ... 

Fig. 12.1. Domain scheme of selected proteins with internal ubiquitin-like domains. Ubiquitin-like domains are indicated by black boxes. Other domains are abbreviated as follows ThiF, NAD-binding domain in ubiq-uitin activating enzymes UAct, 2nd conserved domain in ubiquitin activating enzymes ...

Figure 2. Histone H2A variants from yeast Saccharomyces cerevisiae S.c.), fruit fly Drosophila melanogaster D.m ), and human Homo sapiens H.s.). Two conserved domains distinguish H2A.Z-relatives (boxed regions amino acid sequences in the top). H2A.X possesses a conserved C-terminal stretch of four amino acids. The serine (red) becomes phosphorylated at sites of DNA damage. H2A ( Barr body-deficient ) and marcoH2A are present in mammals...

ExPASy (Expert Protein Analysis System, www.expasy.ch) or the National Centre for Biotechnology Information (NCBI, www.ncbi.nlm.gov) websites. Both websites provide bioinformatics tools, links to sequence databases and extensive bibliographic resources. As an example of the wealth of information available on individual enzymes, at the time of writing a search based on nitrilase in the Entrez protein section of NCBI will recover more than 10000 references to nitrilase enzyme amino acid sequences. These can be rapidly screened online by organism, and the individual entries will have links to amino acid and gene sequence, relevant literature and information on protein features (such as conserved domains). 

Yamauchi E, Kiyonami R, Kanai M, Taniguchi H. 1998. The C-terminal conserved domain of MARCKS is phosphory-lated in vivo by praline-directed protein kinase. Application of ion trap mass spectrometry to the determination of protein phosphorylation sites. J Biol Chem 273 4367. 

Khavari, P.A., Peterson, C.L., Tamkun, J.W., Mendel, D.B., and Crabtree, G.R. (1993) BRGl contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription. Nature 366, 170-174. 

GxG), motif II (YxG), motif III (RFINHxCxPN) and motif IV (ELxFDY where x is any amino acid). The conserved domain folds into several small -sheets that surround a knot-like structure to which additional domains (pre-SET (or nSET), post-SET (or cSET)) or an insertion domain (i-SET) may be added (Figure 2.5). 

The only clinically approved and therefore most studied natural siderophore is des-ferrioxamine B (DFO), and hence it serves as a reference compound in evaluating new biomimetic siderophores. The following discussion will include a short description of several natural hydroxamate siderophore families in separate tables, followed by the various attempts to prepare novel simplified structures that reproduce biological activity. These tables are not intended to cover the entire archive of known siderophores, but merely to allow the reader to observe structural variations, their chemical composition and location as well as conserved domains. 

Like LAR, ANR is a member of the RED protein family. Full details of the protein structure and reaction mechanism are yet to be published. However, Xie et al. compared the A. thaliana (AtANR) and M. truncatula (MtANR) ANR amino acid sequences and recombinant protein activities, and made suggestions on the possible reaction series. The two recombinant proteins showed significantly different kinetic properties, substrate specificities, and cofactor requirements. Although AtANR and MtANR share only 60% sequence identity, some well-conserved domains are evident, in particular the Rossmann dinucleotidebinding domain (GxxGxxG) near the N-termini. However, two amino acid variations did... 

The cyclins were originally defined as proteins that show cyclic concentration variations during the cell cycle (Fig. 13.7). A classifying feature of the cyclins today is the cyc-lin box, a conserved domain of ca. 100 amino acids. Binding to the corresponding CDK takes place via the cyclin box. 

Nixon, B.T. Ronson, C.W. Ausubel, F.M. Two-component regulatory systems responsive to environmental stimuli share strongly conserved domains with the nitrogen assimilation regulatory genes ntrB and ntrC. Proc. Natl. Acad. Sci. USA, 83, 7850-7854 (1986)... 

Even though the roles of IF-2, EF-Tu, EF-G, and RF-3 in protein synthesis are quite different, all four of these proteins share a domain with significant amino acid sequence similarity. Suggest a role for this conserved domain. 

STAT1 is activated by various ligands including cytokines, IFN-a, IFN-y, IL-4, IL-5, IL-13, growth factors and hormones. It has four conserved domains N-terminal, C-terminal, SH2 domain and DNA-binding domain, which is typical of all STAT family members. The SH2 domain is distinct for each STAT and a stable SH2-phosphotyrosine bond is formed after the SH2 domain binds to its specific phosphotyrosine domain. This SH2-pTyr bond is responsible for STAT activation... 

Neame, P.J. Barber, M.J. (1989). Conserved domains in molybdenum hydroxylases. Journal of Biological Chemistry 264,20894-901. 

Monoclonal antibody DO-11 recognizes two adjacent peptides (38 and 39) in the PEPSCAN series, localizing the minimum epitope to the 10 amino acids, 181 arginine to 190 proline. The epitope for this antibody lies in the central part of the molecule, the conserved domain IE at the surface of the mutant p53 antigen. This antibody completely fails to immunoprecipitate p53 in the wild-type conformation (Vojtesek et al., 1995). 

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